Comprehensive Skeletal / Malformation Syndrome Panel

  • bpg-method PLUS
  • bpg-method SEQ
  • bpg-method DEL/DUP

Test code: MA3201

The Blueprint Genetics Comprehensive Skeletal / Malformation Syndrome Panel is a 429 gene test for genetic diagnostics of patients with clinical suspicion of malformations or skeletal syndromes.

Blueprint Genetics (BpG) offers comprehensive genetic diagnostics for malformations. In total the malformation category consists of 32 unique panels including 429 unique genes, all covered by this comprehensive panel. Inherited skeletal diseases are known to be difficult to subtype and divide to categories. This panel covers vast majority of the genes listed in the Nosology 2015 (PMID: 26394607) and all genes in the category (Malformations) therefore providing maximal differential diagnostic power in the field.

About Malformation Syndromes

This panel covers broad spectrum of connective tissue and skeletal disorders leading to syndromes manifesting from isolated defects, growth abnormalities to malformations in the whole body level. Some of the panels cover organ specific malformations such as Hirschsprung disease and gastrointestinal atresias, cerebral cavernous malformations and neurofibromatosis. Genetic diagnostics in these diseases is the most efficient way to subtype the diseases and enable individualized treatment and management decisions. Moreover, detection of causative mutation establishes inheritance mode of the disease in the family which is essential for informed genetic counseling.


Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more:

Genes in the Comprehensive Skeletal / Malformation Syndrome Panel and their clinical significance
Gene Associated phenotypes Inheritance ClinVar HGMD
ABCC6* Pseudoxanthoma elasticum AR 39 285
ACP5 Spondyloenchondrodysplasia with immune dysregulation AR 10 24
ACTA1 Myopathy AD/AR 34 201
ACTB* Baraitser-Winter syndrome AD 27 26
ACTG1* Deafness, Baraitser-Winter syndrome AD 17 37
ACVR1 Fibrodysplasia ossificans progressiva AD 12 18
ADAMTS2 Ehlers-Danlos syndrome AR 3 11
ADAMTS10 Weill-Marchesani syndrome AR 8 13
ADAMTSL2 Geleophysic dysplasia AR 7 26
ADGRG1 Polymicrogyria, bilateral frontoparietal, Polymicrogyris, bilateral perisylvian AR 22
AGPS Rhizomelic chondrodysplasia punctata type 3 AR 4 8
AGRN Myasthenic syndrome, congenital AR 10 10
AKT1 Proteus syndrome, Cowden syndrome AD 3 9
AKT3 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome AD 8 21
ALPL Odontohypophosphatasia, Hypophosphatasia perinatal lethal, infantile, juvenile and adult forms AD/AR 32 270
ALX3 Frontonasal dysplasia type 1 AR 7 7
ALX4 Frontonasal dysplasia type 2, Parietal foramina AD/AR 13 22
AMER1 Osteopathia striata with cranial sclerosis XL 9 34
ANKH Calcium pyrophosphate deposition disease (familial chondrocalcinosis type 2), Craniometaphyseal dysplasia autosomal dominant type AD 12 21
ANO5 Gnathodiaphyseal dysplasia, LGMD2L and distal MMD3 muscular dystrophies AR 42 106
ARFGEF2 Heterotopia, periventricular AR 5 11
ARHGAP31 Adams-Oliver syndrome AD 2 4
ARID1A Coffin-Siris syndrome, Mental retardation AD 11 12
ARID1B Coffin-Siris syndrome, Mental retardation AD 53 126
ARSE* Chondrodysplasia punctata X-linked recessive, brachytelephalangic type (CDPX1) XL 16 46
ARX Lissencephaly, Epileptic encephalopathy, Corpus callosum, agenesis of, with abnormal genitalia, Partington syndrome, Proud syndrome, Hydranencephaly with abnormal genitalia, Mental retardation XL 56 80
ASPA Aspartoacylase deficiency (Canavan disease) AR 19 90
ASPM Microcephaly AR 139 153
ASXL1 Bohring-Opitz syndrome AD 14 27
ATP6V0A2 Cutis laxa, Wrinkly skin syndrome AR 16 52
ATR Cutaneous telangiectasia and cancer syndrome, Seckel syndrome AD/AR 6 13
B3GALNT2 Muscular dystrophy-dystroglycanopathy AR 7 13
B3GALT6 Spondyloepimetaphyseal dysplasia with joint laxity, Ehlers-Danlos syndrome AR 14 22
B4GALT7 Ehlers-Danlos syndrome, progeroid form AR 8 8
BHLHA9 Syndactyly Malik-Percin type, mesoaxial synostotic, with phalangeal reduction, Split hand-foot malformation with long bone deficiency (SHFLD3), Gollop-Wolfgang AR 4 29
BIN1 Myopathy, centronuclear AR 6 15
BMP1 Osteogenesis imperfecta AR 6 11
BMP2 Brachydactyly type A2 AD 1 26
BMP4 Microphthalmia, syndromic, Orofacial cleft AD 9 42
BMPR1A* Polyposis, juvenile intestinal AD 38 108
BMPR1B Acromesomelic dysplasia, Demirhan, Brachydactyly C/Symphalangism-like pheno, Brachydactyly type A2 AD/AR 11 13
BRWD3 Mental retardation XL 6 9
CA2 Osteopetrosis, with renal tubular acidosis AR 8 30
CANT1 Desbuquois dysplasia AR 17 25
CAPN3 Muscular dystrophy, limb-girdle, Eosinophilic myositis AR 102 400
CASK Mental retardation and microcephaly with pontine and cerebellar hypoplasia, FG syndrome, Mental retardation XL 43 80
CASR Hypocalcemia, Neonatal hyperparathyroidism, Familial Hypocalciuric hypercalcemia with transient Neonatal hyperparathyroidism AD/AR 78 392
CBS Homocystinuria due to cystathionine beta-synthase deficiency AR 51 192
CCM2 Cerebral cavernous malformations AD 14 79
CCND2 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome AD 7 10
CDC6 Meier-Gorlin syndrome (Ear-patella-short stature syndrome) AR 1 3
CDK5RAP2 Microcephaly AR 15 15
CDKN1C Beckwith-Wiedemann syndrome, IMAGE syndrome AD 25 79
CDON Holoprosencephaly AD 7 10
CDT1 Meier-Gorlin syndrome (Ear-patella-short stature syndrome) AR 6 8
CENPF Ciliary dyskinesia -Lethal Ciliopathy AR 8 6
CENPJ Seckel syndrome, Microcephaly AR 23 6
CEP63 Seckel syndrome AR 4 2
CEP152 Seckel syndrome, Microcephaly AR 13 17
CEP164 Nephronophthisis AR 7 8
CFL2 Nemaline myopathy AR 2 3
CHAT Myasthenic syndrome, congenital AR 14 68
CHD7 Isolated gonadotropin-releasing hormone deficiency, CHARGE syndrome AD 128 746
CHD8 Autism AD 10 37
CHKB Muscular dystrophy, congenital, megaconial AR 5 22
CHRNA1 Myasthenic syndrome, congenital AD/AR 19 32
CHRNB1 Myasthenic syndrome AD/AR 5 8
CHRND Myasthenic syndrome AD/AR 12 19
CHRNE Myasthenic syndrome AD/AR 26 121
CHRNG Multiple pterygium syndrome, Escobar syndrome AR 11 29
CHST3 Spondyloepiphyseal dysplasia with congenital joint dislocations (recessive Larsen syndrome) AR 13 35
CHST14 Ehlers-Danlos syndrome, musculocontractural AR 10 21
CLCN5 Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis, Hypophosphatemic rickets,, Nephrolithiasis, I, Dent disease XL 37 255
CLCN7 Osteopetrosis AD/AR 9 91
COL1A1 Ehlers-Danlos syndrome, Caffey disease, Osteogenesis imperfecta type 1, Osteogenesis imperfecta type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4 AD 120 883
COL1A2 Ehlers-Danlos syndrome, cardiac valvular form, Osteogenesis imperfecta type 1, Osteogenesis imperfecta type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4 AD/AR 79 473
COL2A1 Avascular necrosis of femoral head, Rhegmatogenous retinal detachment, Epiphyseal dysplasia, with myopia and deafness, Czech dysplasia, Achondrogenesis type 2, Platyspondylic dysplasia Torrance type, Hypochondrogenesis, Spondyloepiphyseal dysplasia congenital (SEDC), Spondyloepimetaphyseal dysplasia (SEMD) Strudwick type, Kniest dysplasia, Spondyloperipheral dysplasia, Mild SED with premature onset arthrosis, SED with metatarsal shortening, Stickler syndrome type 1 AD 106 537
COL3A1 Ehlers-Danlos syndrome AD 452 617
COL4A1 Schizencephaly, Anterior segment dysgenesis with cerebral involvement, Retinal artery tortuosity, Porencephaly, Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, Brain small vessel disease AD 27 88
COL4A2 Hemorrhage, intracerebral AD 5 12
COL4A4 Alport syndrome AD/AR 17 170
COL5A1 Ehlers-Danlos syndrome AD 43 133
COL5A2 Ehlers-Danlos syndrome AD 12 23
COL6A1 Bethlem myopathy, Ullrich congenital muscular dystrophy AD/AR 46 95
COL6A2 Epilepsy, progressive myoclonic, Bethlem myopathy, Myosclerosis, congenital, Ullrich congenital muscular dystrophy AD/AR 65 134
COL6A3 Bethlem myopathy, Dystonia, Ullrich congenital muscular dystrophy AD/AR 36 105
COL9A1 Stickler syndrome recessive type, Multiple epiphyseal dysplasia type 6 (EDM6) AR 3 4
COL9A2 Stickler syndrome, Multiple epiphyseal dysplasia type 2 (EDM2) AD/AR 5 12
COL9A3 Multiple epihyseal dysplasia type 3 (EDM3) AD/AR 3 16
COL10A1 Metaphyseal chondrodysplasia, Schmid AD 20 50
COL11A1 Marshall syndrome, Fibrochondrogenesis, Stickler syndrome type 2 AD/AR 18 76
COL11A2 Weissenbacher-Zweymuller syndrome, Deafness, Otospondylomegaepiphyseal dysplasia, Fibrochondrogenesis, Stickler syndrome type 3 (non-ocular) AD/AR 17 51
COLQ Myasthenic syndrome, congenital AR 12 66
COMP Pseudoachondroplasia, Multiple ephiphyseal dysplasia AD 33 182
CREBBP Rubinstein-Taybi syndrome AD 103 332
CRTAP Osteogenesis imperfecta type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4 AR 11 24
CSPP1 Jeune asphyxiating thoracic dystrophy, Joubert syndrome AR 22 23
CTSK Pycnodysostosis AR 7 53
CUL4B Mental retardation, syndromic, Cabezas XL 9 34
CUL7 3-M syndrome, Yakut short stature syndrome AR 18 68
CYP27B1 Vitamin D-dependent rickets AR 20 75
DCX Lissencephaly, Subcortical laminal heterotopia XL 117 138
DHCR7 Smith-Lemli-Opitz syndrome AR 42 194
DHCR24 Desmosterolosis AR 6 8
DIS3L2* Perlman syndrome AR 6 9
DLL3 Spondylocostal dysostosis AR 9 21
DLL4 Adams-Oliver syndrome AD 9 10
DLX3 Amelogenesis imperfecta, Trichodontoosseous syndrome AD 2 6
DNM2 Myopathy, Lethal akinesia and musculoskeletal abnormalities, with brain and retinal hemorrhages, Charcot-Marie-Tooth disease AD/AR 23 44
DNMT3A Tatton-Brown-Rahman syndrome AD 11 18
DOCK6 Adams-Oliver syndrome AR 13 19
DOK7 Myasthenic syndrome, congenital AR 15 68
DPAGT1 Congenital disorder of glycosylation, Myasthenic syndrome, congenital AR 12 28
DVL1 Robinow syndrome AD 9 13
DYM Dyggve-Melchior-Clausen dysplasia, Smith-McCort dysplasia AR 20 28
DYNC1H1 Spinal muscular atrophy, Charcot-Marie-Tooth disease, Mental retardation AD 34 53
DYNC2H1 Short -rib thoracic dysplasia with or without polydactyly type 1, Short -rib thoracic dysplasia with or without polydactyly type 3, Asphyxiating thoracic dysplasia (ATD; Jeune), SRPS type 2 (Majewski) AR/Digenic 34 98
DYRK1A Mental retardation AD 40 50
EBP Chondrodysplasia punctata, Male EBP disorder with neurologic defects (MEND) XL 43 89
ECEL1 Arthrogryposis AR 18 27
EDN3 Hirschsprung disease, Central hypoventilation syndrome, congenital, Waardenburg syndrome AD/AR 6 21
EDNRB Hirschsprung disease, ABCD syndrome, Waardenburg syndrome AD/AR 5 62
EFEMP2 Cutis laxa AR 11 15
EFNB1 Craniofrontonasal dysplasia XL 15 115
EFTUD2 Mandibulofacial dysostosis with microcephaly, Esophageal atresia, syndromic AD 16 88
EGR2 Neuropathy, Dejerine-Sottas disease, Charcot-Marie-Tooth disease AD/AR 12 23
EIF2AK3 SED, Wolcott-Rallison type AR 7 71
EIF2B5 Leukoencephalopathy with vanishing white matter, Ovarioleukodystrophy AR 14 95
ELN Cutis laxa, Supravalvular aortic stenosis AD 67 104
EMD Emery-Dreifuss muscular dystrophy XL 28 111
EMX2 Schizencephaly AD 4 6
ENAM Amelogenesis imperfecta AR 3 18
ENPP1 Arterial calcification, Hypophosphatemic rickets AR 17 72
EOGT Adams-Oliver syndrome AR 3 3
EP300 Rubinstein-Taybi syndrome AD 21 43
ERCC5 Xeroderma pigmentosum, Xeroderma pigmentosum/Cockayne syndrome AR 17 51
ERCC6 Xeroderma Pigmentosum-Cockayne Syndrome, De Sanctis-Cacchione syndrome AD/AR 37 91
ERCC8 UV-sensitive syndrome, Cockayne syndrome AR 9 39
ESCO2 SC phocomelia syndrome, Roberts syndrome AR 29 30
EVC Weyers acrofacial dysostosis, Ellis-van Creveld syndrome AD/AR 7 77
EVC2 Ellis-van Creveld syndrome, Weyers acrodental dysostosis AD/AR 23 66
EXOSC3 Pontocerebellar hypoplasia AR 9 18
EXT1 Multiple cartilagenious exostoses 1 AD 28 479
EXT2 Multiple cartilagenious exostoses 2 AD 20 230
EYA1 Otofaciocervical syndrome, Branchiootic syndrome, Branchiootorenal syndrome AD 33 186
EZH2 Weaver syndrome AD 14 36
FAM20A Amelogenesis imperfecta (Enamel-renal syndrome) AR 9 40
FAM20C Hypophosphatemia, hyperphosphaturia, dental anomalies, intracerebral calcifications and osteosclerosis (Raine syndrome) AR 13 22
FAM83H Amelogenesis imperfecta AD 13 27
FANCB Fanconi anemia XL 7 14
FANCC Fanconi anemia AR 34 34
FBLN5 Cutis laxa, Macular degeneration, age-related AD/AR 13 21
FBN1 MASS syndrome, Shprintzen-Goldberg syndrome, Marfan syndrome, Acromicric dysplasia, Geleophysic dysplasia, Weill-Marchesani syndrome AD 519 2056
FBN2 Congenital contractural arachnodactyly (Beals syndrome) AD 30 85
FGD1 Aarskog-Scott syndrome, Mental retardation, syndromic XL 18 42
FGF3 Deafness, congenital with inner ear agenesis, microtia, and microdontia AR 12 20
FGF8 Hypogonadotropic hypogonadism AD/Digenic 10 28
FGF23 Tumoral calcinosis, hyperphosphatemic, Hypophosphatemic rickets AD/AR 7 16
FGFR1 Pfeiffer syndrome, Trigonocephaly, Hypogonadotropic hypogonadism, Osteoglophonic Dwarfism - Craniostenosis, Hartsfield syndrome AD/Digenic/Multigenic 41 232
FGFR2 Apert syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome, Lacrimoauriculodentodigital syndrome, Beare-Stevenson cutis gyrata syndrome, Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis, Craniofacial-skeletal-dermatological dysplasia, Crouzon syndrome, Bent bone dysplasia AD 47 145
FGFR3 Lacrimoauriculodentodigital syndrome, Muenke syndrome, Crouzon syndrome with acanthosis nigricans, Camptodactyly, tall stature, and hearing loss (CATSHL) syndrome, Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia type 1, Thanatophoric dysplasia type 2, SADDAN AD/AR 47 68
FH Hereditary leiomyomatosis and renal cell cancer AD/AR 89 161
FHL1* Myopathy with postural muscle atrophy, Emery-Dreifuss muscular dystrophy, Reducing bod myopathy XL 18 47
FKBP10 Bruck syndrome type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4 AR 17 27
FKBP14 Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss AR 4 4
FKRP Muscular dystrophy-dystroglycanopathy AR 31 99
FKTN Muscular dystrophy-dystroglycanopathy, Dilated cardiomyopathy (DCM), Muscular dystrophy-dystroglycanopathy (limb-girdle) AD/AR 28 51
FLNA Frontometaphyseal dysplasia, Osteodysplasty Melnick-Needles, Otopalatodigital syndrome type 1, Otopalatodigital syndrome type 2, Terminal osseous dysplasia with pigmentary defects XL 86 209
FLNB Larsen syndrome (dominant), Atelosteogenesis type 1, Atelosteogenesis type 3, Spondylo-carpal-tarsal dyspasia AD/AR 38 98
FOXH1 Congenital heart malformations, Holoprosencephaly AD 32
FOXL2 Premature ovarian failure, Blepharophimosis, epicanthus inversus, and ptosis AD 69 203
FREM1 Bifid nose, Manitoba oculotrichoanal syndrome, Trigonocephaly AD/AR 8 23
GAA Glycogen storage disease AR 79 503
GBA* Gaucher disease AR 73 446
GBE1 Glycogen storage disease AR 25 69
GDF5 Multiple synostoses syndrome, Fibular hypoplasia and complex brachydactyly, Acromesomelic dysplasia, Hunter-Thompson, Symphalangism, proximal, Chondrodysplasia, Brachydactyly type A2, Brachydactyly type C, Grebe dysplasia AD/AR 22 52
GFAP Alexander disease AD 110 112
GFPT1 Myasthenic syndrome, congenital AR 6 33
GH1* Isolated growth hormone deficiency, Kowarski syndrome AD/AR 24 98
GHR Growth hormone insensitivity syndrome (Laron syndrome) AD/AR 32 100
GHRHR Isolated growth hormone deficiency AR 13 47
GJA1* Oculodentodigital dysplasia mild type, Oculodentodigital dysplasia severe type, Syndactyly type 3 AD 23 103
GLE1 Lethal congenital contracture syndrome, Arthrogryposis, lethal, with anterior horn cell disease AR 4 9
GLI2 Culler-Jones syndrome AD 16 74
GLI3 Acrocallosal syndrome, Pallister-Hall syndrome, Grieg cephalopolysndactyly syndrome, Postaxial polydactyly type A, Preaxial polydactyly type 3, Preaxial polydactyly type 4 AD 49 221
GMPPB Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), Limb-girdle muscular dystrophy-dystroglycanopathy AR 13 26
GNAS McCune-Albright syndrome, Progressive osseous heteroplasia, Pseudohypoparathyroidism, Albright hereditary osteodystrophy AD 45 257
GNPAT Rhizomelic chondrodysplasia punctata, rhizomelic AR 8 14
GPC3 Simpson-Golabi-Behmel syndrome XL 22 65
GPSM2 Deafness, Chudley-McCullough syndrome AR 10 11
GRIA3 Mental retardation XL 9 17
HDAC8 Cornelia de Lange syndrome XL 18 40
HEPACAM Megalencephalic leukoencephalopathy with subcortical cysts, remitting AD/AR 9 23
HESX1 Septooptic dysplasia, Pituitary hormone deficiency, combined AR/AD 11 25
HOXA13 Hand-foot-uterus syndrome, Hand-foot-genital syndrome, Guttmacher syndrome AD 8 22
HOXD13 Brachydactyly-syndactyly syndrome, Synopolydactyly, Syndactyly, Synopolydactyly with clefting, Brachydactyly type D AD/AR 18 38
HSPG2 Schwartz-Jampel syndrome, Dyssegmental dysplasia Silverman-Handmaker type, Dyssegmental dysplasia Rolland-Desbuquis type AD/AR 15 52
HUWE1 Mental retardation, syndromic, Turner XL 8 31
IFT80 Short -rib thoracic dysplasia with or without polydactyly, Asphyxiating thoracic dysplasia (ATD; Jeune) AR 5 7
IFT122* Sensenbrenner syndrome, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 1, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 2 AR 9 13
IFT140 Short -rib thoracic dysplasia with or without polydactyly, Asphyxiating thoracic dysplasia (ATD; Jeune) AR 14 46
IFT172 Retinitis pigmentosa, Short -rib thoracic dysplasia with or without polydactyly, Asphyxiating thoracic dysplasia (ATD; Jeune) AR 18 21
IGF1 Insulin-like growth factor I deficiency AR 4 12
IGF1R Insulin-like growth factor I, resistance AD/AR 5 62
IGFALS Insulin-like growth factor-binding protein, acid-labile subunit, deficiency AR 5 28
IHH Acrocapitofemoral dysplasia, Brachydactyly, Syndactyly type Lueken AD/AR 11 17
IKBKG* Incontinentia pigmenti, Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, Immunodeficiency, Invasive pneumococcal disease, recurrent, isolated, Osteopetrosis with ectodermal dysplasia and immune defect (OLEDAID) XL 30 141
INSR Hyperinsulinemic hypoglycemia, familial, Rabson-Mendenhall syndrome, Donohoe syndrome AD/AR 35 175
IRF6 Orofacial cleft, Popliteal pterygium syndrome, van der Woude syndrome AD 26 327
IRS1 Diabetes mellitus, noninsulin-dependent AD/AR 2 23
ISPD Muscular dystrophy-dystroglycanopathy AR 20 42
KAT6B Ohdo syndrome, SBBYS variant, Genitopatellar syndrome AD 23 53
KBTBD13 Nemaline myopathy AD 3 6
KDM6A Kabuki syndrome XL 18 48
KIAA0196 Spastic paraplegia, Ritscher-Schinzel syndrome (3C syndrome) AD/AR 7 14
KIF1BP Goldberg-Shprintzen megacolon syndrome AR 5
KIF7 Acrocallosal syndrome, Hydrolethalus syndrome, Al-Gazali-Bakalinova syndrome, Joubert syndrome AR/Digenic 13 39
KIF11 Microcephaly AD 17 58
KIT Gastrointestinal stromal tumor AD 27 111
KLHL40 Nemaline myopathy AR 5 24
KMT2D Kabuki syndrome AD 136 558
KRAS* Noonan syndrome, Cardiofaciocutaneous syndrome AD 46 38
KRIT1 Cerebral cavernous malformations AD 22 247
L1CAM Mental retardation, aphasia, shuffling gait, and adducted thumbs (MASA) syndrome, Hydrocephalus due to congenital stenosis of aqueduct of Sylvius, Spastic, CRASH syndrome, Corpus callosum, partial agenesis XL 37 286
LAMA2 Muscular dystrophy, congenital merosin-deficient AR 72 225
LAMP2 Danon disease XL 46 81
LARGE Muscular dystrophy-dystroglycanopathy AR 15 22
LBR Pelger-Huet anomaly, Reynolds syndrome, Greenberg/HEM skeletal dysplasia, Hydrops-ectopic calcification-moth-eaten skeletal dysplasia AD 15 22
LEMD3 Buschke-Ollendorff syndrome, Osteopoikilosis AD 9 29
LHX3 Pituitary hormone deficiency, combined AR 9 14
LHX4 Pituitary hormone deficiency, combined AD 9 17
LIFR Stuve-Wiedemann dysplasia, Schwartz-Jampel type 2 syndrome AR 9 28
LIG4 Severe combined immunodeficiency with sensitivity to ionizing radiation, LIG4 syndrome AR 8 36
LMNA Heart-hand syndrome, Slovenian, Limb-girdle muscular dystrophy, Muscular dystrophy, congenital, LMNA-related, Lipodystrophy (Dunnigan), Emery-Dreiffus muscular dystrophy, Malouf syndrome, Dilated cardiomyopathy (DCM), Mandibuloacral dysplasia type A, Progeria Hutchinson-Gilford type AD/AR 183 458
LMX1B Nail-patella syndrome AD 18 190
LRP4 Cenani-Lenz syndactyly syndrome, Sclerosteosis, Myasthenic syndrome, congenital AD/AR 12 23
LRP5* Van Buchem disease, Osteoporosis-pseudoglioma syndrome, Hyperostosis, endosteal, Osteosclerosis, Exudative vitreoretinopathy, Osteopetrosis late-onset form type 1, LRP5 primary osteoporosis AD/AR/Digenic 36 163
LTBP2 Weill-Marchesani syndrome, Microspherophakia and/or megalocornea, with ectopia lentis and with or without secondary glaucoma, Glaucoma, primary congenital AR 21 23
MASP1 3MC syndrome AR 7 14
MATN3 Spondyloepimetaphyseal dysplasia Matrilin type, Multiple epiphyseal dysplasia type 5 (EDM5) AD/AR 8 25
MBD5 Mental retardation AD 21 72
MCPH1 Microcephaly AR 17 29
MED12 Ohdo syndrome, Mental retardation, with Marfanoid habitus, FG syndrome, Opitz-Kaveggia syndrome, Lujan-Fryns syndrome XL 17 19
MEF2C Mental retardation AD 25 66
MID1* Opitz GBBB syndrome XL 18 94
MITF Renal cell carcinoma with or without malignant melanoma, Tietz albinism-deafness syndrome, Waardenburg syndrome, Melanoma, cutaneous malignant AD 15 50
MLC1 Megalencephalic leukoencephalopathy with subcortical cysts AR 17 111
MMP9 Metaphyseal anadysplasia AR 1 12
MPZ Neuropathy, Roussy-Levy syndrome, Dejerine-Sottas disease, Charcot-Marie-Tooth disease AD 74 235
MRE11A Ataxia-telangiectasia-like disorder-1 AR 25 38
MSX2* Parietal foramina, Parietal foramina with cleidocranial dysplasia, Craniosynostosis Boston type AD 9 24
MTM1 Myopathy, centronuclear XL 152 284
MUSK Myasthenic syndrome, congenital AR 10 17
MYBPC1 Arthrogryposis, Lethal congenital contractural syndrome AD/AR 4 7
MYH2 Inclusion body myopathy AD 10 20
MYH3 Arthrogryposis AD 14 31
MYH7 Hypertrophic cardiomyopathy (HCM), Myopathy, myosin storage, Myopathy, distal, Dilated cardiomyopathy (DCM) AD 285 748
NALCN Neuroaxonal neurodegeneration, infantile, with facial dysmophism, Congenital contractures of the limbs and face, hypotonia, and developmental delay AD/AR 23 28
NDE1 Microhydranencephaly, Lissencephaly AR 10 14
NEB* Nemaline myopathy AR 34 262
NEK1 Short -rib thoracic dysplasia with or without polydactyly, SRPS type 2 (Majewski) AR/Digenic 8 10
NF1* Watson syndrome, Neurofibromatosis, Neurofibromatosis-Noonan syndrome AD 261 2607
NF2 Schwannomatosis, Neurofibromatosis AD 24 423
NFIX Marshall-Smithsyndrome AD 27 51
NHEJ1 Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation AR 8 13
NIPBL Cornelia de Lange syndrome AD 246 404
NODAL Heterotaxy, visceral AD 4 23
NOG Tarsal-carpal coalition syndrome, Multiple synostosis syndrome, Stapes ankylosis with broad thumb and toes (Teunissen-Cremers syndrome), Symphalangism, proximal, Brachydactyly type B2 AD 18 61
NOTCH1 Aortic valve disease AD 28 72
NOTCH2* Alagille syndrome, Hajdu-Cheney syndrome AD 21 56
NPR2 Acromesomelic dysplasia type Maroteaux, Epiphyseal chondrodysplasia, Miura, Short stature with nonspecific skeletal abnormalities AD/AR 14 61
NR5A1 Adrenocortical insufficiency, Premature ovarian failure, 46,XY sex reversal AD/AR 21 137
NRG1 Nonsyndromic Hirschsprung disease AD/AR 1 16
NSD1 Sotos syndrome, Weaver syndrome, Beckwith-Wiedemann syndrome AD 212 461
NSDHL Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD syndrome), CK syndrome XL 15 28
OBSL1 3-M syndrome AR 9 22
OCRL Lowe syndrome, Dent disease XL 33 251
OFD1 Simpson-Golabi-Behmel syndrome, Retinitis pigmentosa, Orofaciodigital syndrome, Joubert syndrome XL 129 148
OPHN1 Mental retardation, with cerebellar hypoplasia and distinctive facial appearance XL 13 34
ORC1 Meier-Gorlin syndrome (Ear-patella-short stature syndrome) AR 9 9
ORC4 Meier-Gorlin syndrome (Ear-patella-short stature syndrome) AR 13 5
ORC6 Meier-Gorlin syndrome (Ear-patella-short stature syndrome) AR 5 5
OTX2 Microphthalmia, syndromic, Pituitary hormone deficiency, combined, Retinal dystrophy, early-onset, and pituitary dysfunction AD 16 65
P3H1 Osteogenesis imperfecta AR 12 33
PAFAH1B1 Lissencephaly, Subcortical laminar heterotopia AD 106 165
PAPSS2 Brachyolmia 4 with mild epiphyseal and metaphyseal changes, SEMD PAPPS2 type AR 10 21
PAX3 Craniofacial-deafness-hand syndrome, Waardenburg syndrome AD/AR 20 135
PAX6 Aniridia, cerebellar ataxia, and mental retardation (Gillespie syndrome), Keratitis, Coloboma, ocular, Cataract with late-onset corneal dystrophy, Morning glory disc anomaly, Foveal hypoplasia, Aniridia, Optic nerve hypoplasia, Peters anomaly AD 49 461
PCNT Microcephalic osteodysplastic primordial dwarfism AR 30 82
PDCD10 Cerebral cavernous malformations AD 10 76
PEX7 Refsum disease, Rhizomelic CDP type 1 AR 17 51
PHEX Hypophosphatemic rickets XL 75 411
PHF6 Borjeson-Forssman-Lehmann syndrome XL 15 27
PIEZO2* Marden-Walker syndrome, Distal arthrogryposis AD 21 24
PIGA* Multiple congenital anomalies-hypotonia-seizures syndrome XL 19 14
PIK3CA* Cowden syndrome, CLOVES AD 30 44
PITX2 Axenfeld-Rieger syndrome, Ring dermoid of cornea, Iridogoniodysgenesis, Peters anomaly AD 13 85
PLOD1 Ehlers-Danlos syndrome AR 16 37
PLOD2 Bruck syndrome, Osteogenesis imperfecta type 3 AR 4 11
PMM2 Congenital disorder of glycosylation AR 37 119
PNKP Epileptic encephalopathy, early infantile, Ataxia-oculomotor AR 21 16
POLR1C Treacher Collins syndrome AR 13 18
POMGNT1 Muscular dystrophy-dystroglycanopathy AR 55 73
POMT1 Muscular dystrophy-dystroglycanopathy AR 31 81
POMT2 Muscular dystrophy-dystroglycanopathy AR 28 48
POR Disordered steroidogenesis due to cytochrome p450 oxidoreductase deficiency, Antley-Bixler syndrome AR 12 84
POU1F1 Pituitary hormone deficiency, combined AR 19 42
PPIB Osteogenesis imperfecta type 2, Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4 AR 6 11
PQBP1 Renpenning syndrome XL 8 17
PRKAR1A Myxoma, intracardiac, Acrodysostosis, Pigmented nodular adrenocortical disease, Carney complex AD 50 173
PROP1 Pituitary hormone deficiency, combined AR 19 34
PTCH1 Basal cell nevus syndrome AD 46 348
PTEN* Bannayan-Riley-Ruvalcaba syndrome, Lhermitte-Duclos syndrome, Cowden syndrome AD 192 564
PTH1R Metaphyseal chondrodysplasia Jansen type, Failure of tooth eruption, Eiken dysplasia, Blomstrand dysplasia AD/AR 13 40
PTPN11 LEOPARD syndrome, Noonan syndrome, Metachondromatosis AD 122 129
PYCR1 Cutis laxa AR type 2B AR 12 34
RAB3GAP1 Warburg micro syndrome AR 16 58
RAB3GAP2 Warburg micro syndrome, Martsolf syndrome AR 7 11
RAB39B Waisman parkinsonism-mental retardation syndrome, Mental retardation XL 4 11
RAF1 LEOPARD syndrome, Noonan syndrome, Dilated cardiomyopathy (DCM) AD 37 42
RAPSN Myasthenic syndrome, congenital AR 18 57
RARS2 Pontocerebellar hypoplasia AR 17 30
RASA1 Parkes Weber syndrome, Capillary malformation-arteriovenous malformation, Spinal arteriovenous anomalies AD 18 113
RBBP8 Seckel syndrome, Jawad syndrome AR 4 5
RBPJ* Adams-Oliver syndrome AD 2 3
RECQL4 Baller-Gerold syndrome, RAPADILINO syndrome, Rothmund-Thomson syndrome AR 34 92
RELN Lissencephaly, Epilepsy, familial temporal lobe AD/AR 17 31
RET Hirschsprung disease, Central hypoventilation syndrome, congenital, Pheochromocytoma, Medullary thyroid carcinoma, Multiple endocrine neoplasia AD/AR 80 405
RMRP Cartilage-hair hypoplasia, Metaphyseal dysplasia without hypotrichosis, Anauxetic dysplasia AR 24 119
RNU4ATAC Roifman syndrome, Microcephalic osteodysplastic primordial dwarfism type 1, Microcephalic osteodysplastic primordial dwarfism type 3 AR 15 18
ROR2 Robinow syndrome recessive type, Brachydactyly type B AD/AR 18 37
RUNX2 Cleidocranial dysplasia, Metaphyseal dysplasia with maxillary hypoplasia AD 19 203
RYR1 Central core disease, Malignant hyperthermia, Minicore myopathy with external ophthalmoplegia, Centronuclear myopathy, Minicore myopathy, Multicore myopathy AD/AR 123 563
SBDS* Aplastic anemia, Shwachman-Diamond syndrome, Severe spondylometaphyseal dysplasia AD/AR 12 88
SCO2 Leigh syndrome, Hypertrophic cardiomyopathy (HCM), Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency, Myopia AR 17 32
SELENON Muscular dystrophy, rigid spine, Myopathy, congenital, with fiber- disproportion AR 16 50
SERPINF1 Osteogenesis imperfecta type 3, Osteogenesis imperfecta type 4 AR 7 29
SERPINH1 Osteogenesis imperfecta type 3 AR 3 5
SF3B4 Acrofacial dysostosis 1, Nager AD 25 33
SHH Holoprosencephaly, Microphthalmia with coloboma AD 29 212
SHOX* Leri-Weill dyschondrosteosis, Langer mesomelic dysplasia, Short stature XL/PAR 23 366
SIL1 Marinesco-Sjogren syndrome AR 14 49
SIX3 Holoprosencephaly AD 11 82
SIX5 Branchiootorenal syndrome AD 3 7
SKI Shprintzen-Goldberg syndrome AD 15 20
SLC12A6 Agenesis of the corpus callosum with peripheral neuropathy (Andermann syndrome) AR 12 17
SLC26A2 Diastrophic dysplasia, Atelosteogenesis type 2, De la Chapelle dysplasia, Recessive Multiple Epiphyseal dysplasia, Achondrogenesis type 1B AR 32 51
SLC29A3 Histiocytosis-lymphadenopathy plus syndrome, Dysosteosclerosis AR 17 22
SLC34A3 Hypophosphatemic rickets with hypercalciuria AR 10 36
SLC39A13 Spondylodysplastic Ehlers-Danlos syndrome AR 2 7
SLCO2A1 Hypertrophic osteoarthropathy AD/AR 9 46
SMAD3 Aneurysms-osteoarthritis syndrome, Loeys-Dietz syndrome AD 26 50
SMAD4 Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Polyposis, juvenile intestinal, Myhre dysplasia, Hereditary hemorrhagic telangiectasia AD 119 128
SMARCA2 Nicolaides-Baraitser syndrome AD 24 67
SMARCA4 Rhabdoid tumor predisposition syndrome AD 19 42
SMARCAL1 Schimke immunoosseous dysplasia AR 9 70
SMARCB1 Schwannomatosis, Rhabdoid tumor predisposition syndrome AD 17 115
SMC1A Cornelia de Lange syndrome XL 39 54
SMC3 Cornelia de Lange syndrome AD 14 16
SOS1 Noonan syndrome AD 41 66
SOX2* Microphthalmia, syndromic AD 24 94
SOX3 Panhypopituitarism XL 3 26
SOX9 Campomelic dysplasia, 46,XY sex reversal, Brachydactyly with anonychia (Cooks syndrome) AD 24 135
SOX10 Peripheral demyelinating neuropathy, central dysmyelination, Waardenburg syndrome, and Hirschsprung disease AD 31 119
SPRED1 Legius syndrome AD 12 71
SRCAP Floating-Harbor syndrome AD 7 24
SRPX2 Rolandic epilepsy, mental retardation, and speech dyspraxia XL 1 3
SRY 46,XX disorder of sex development, 46,XY disorder of sex development YL 22 102
STAT5B* Growth hormone insensitivity with immunodeficiency AR 5 11
STIL Microcephaly AR 7 9
SYN1 Epilepsy, with variable learning disabilities and behavior disorders XL 7 5
TBX3 Ulnar-Mammary syndrome AD 5 21
TBX19 Adrenocorticotropic hormone deficiency AR 5 26
TCF12 Craniosynostosis AD 13 52
TCIRG1 Osteopetrosis, severe neonatal or infantile forms (OPTB1) AR 9 127
TCOF1 Treacher Collins syndrome AD 17 303
TCTN3 Orofaciodigital syndrome (Mohr-Majewski syndrome), Joubert syndrome AR 8 10
TGFB1 Diaphyseal dysplasia Camurati-Engelmann AD 11 28
TGFB2 Loeys-Dietz syndrome AD 15 24
TGFB3 Loeys-Dietz syndrome (Reinhoff syndrome), Arrhythmogenic right ventricular dysplasia AD 8 18
TGFBR1 Loeys-Dietz syndrome AD 25 67
TGFBR2 Loeys-Dietz syndrome AD 54 130
TGIF1 Holoprosencephaly AD 7 27
TK2 Mitochondrial DNA depletion syndrome AR 38 44
TMEM5 Muscular dystrophy-dystroglycanopathy AR 8 7
TMEM43 Arrhythmogenic right ventricular dysplasia, Emery-Dreifuss muscular dystrophy AD 5 15
TNFRSF11A Familial expansile osteolysis, Paget disease of bone, Osteopetrosis, severe neonatal or infantile forms (OPTB1) AD/AR 8 22
TNFRSF11B Paget disease of bone, juvenile AR 8 21
TNNI2 Arthrogryposis multiplex congenita AD 4 11
TNNT1 Nemaline myopathy AR 2 5
TNXB* Ehlers-Danlos syndrome AR 8 26
TP63 Rapp-Hodgkin syndrome, Orofacial cleft, ADULT syndrome, Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome, Ankyloblepharon-ectodermal defects-cleft lip/palate, Split-hand/foot malformation, Limb-mammary syndrome AD 38 114
TPM2 CAP myopathy, Nemaline myopathy, Arthrogryposis, distal AD 11 37
TPM3* CAP myopathy, Nemaline myopathy, Myopathy, congenital, with fiber- disproportion AD 18 26
TRAPPC2* Spondyloepiphyseal dysplasia tarda XL 12 54
TRPS1 Trichorhinophalangeal syndrome type 1, Trichorhinophalangeal syndrome type 3 AD 18 127
TRPV4 Metatropic dysplasia, Spondyloepiphyseal dysplasia Maroteaux type, Parastremmatic dwarfism, Hereditary motor and sensory neuropathy, Spondylometaphyseal dysplasia Kozlowski type, Spinal muscular atrophy, Charcot-Marie-Tooth disease, Brachyolmia (autosomal dominant type), Familial Digital arthropathy with brachydactyly AD 53 71
TSC1 Lymphangioleiomyomatosis, Tuberous sclerosis AD 61 306
TSC2 Lymphangioleiomyomatosis, Tuberous sclerosis AD 141 977
TSEN2 Pontocerebellar hypoplasia AR 6 4
TSEN54 Pontocerebellar hypoplasia AR 16 20
TTC7A Gastrointestinal defects and immunodeficiency syndrome AR 18 39
TTC21B Short-rib thoracic dysplasia, Nephronophthisis, Asphyxiating thoracic dysplasia (ATD; Jeune) AR 6 47
TTR Dystransthyretinemic hyperthyroxinemia, Amyloidosis, hereditary, transthyretin-related AD 51 138
TUBA1A* Lissencephaly AD 33 62
TUBA8 Polymicrogyria with optic nerve hypoplasia AR 1 1
TUBB2B* Polymicrogyria, asymmetric AD 12 29
TUBB3* Fibrosis of extraocular muscles, congenital, Cortical dysplasia, complex, with other brain malformations AD/AR 18 23
TWIST1 Saethre-Chotzen syndrome, Robinow-Sorauf syndrome, Craniosynostosis AD 14 188
TXNL4A Burn-McKeown syndrome AR 18 10
TYROBP Nasu-Hakola disease, Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy AR 8 14
UBE2A Mental retardation, syndromic, Nascimento XL 4 21
UPF3B Mental retardation, syndromic XL 5 16
VDR Vitamin D-dependent rickets AD/AR 17 67
VLDLR Cerebellar ataxia, mental retardation, and dysequilibrium syndrome AR 9 21
VPS33B Arthrogryposis - renal dysfunction - cholestasis AD/AR 9 53
VRK1 Pontocerebellar hypoplasia AR 6 8
WDR19 Retinitis pigmentosa, Nephronophthisis, Short -rib thoracic dysplasia with or without polydactyly, Senior-Loken syndrome, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 1, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 2, Asphyxiating thoracic dysplasia (ATD; Jeune) AD/AR 16 25
WDR34 Short -rib thoracic dysplasia with or without polydactyly, Asphyxiating thoracic dysplasia (ATD; Jeune) AR 10 15
WDR35 Cranioectodermal dysplasia (Levin-Sensenbrenner) type 1, Cranioectodermal dysplasia (Levin-Sensenbrenner) type 2, Short rib-polydactyly syndrome type 5 AR 15 24
WDR62 Microcephaly AR 24 38
WISP3 Arthropathy, progressive pseudorheumatoid, of childhood, Spondyloepiphyseal dysplasia tarda with progressive arthropathy AR 13 68
WNT5A Robinow syndrome AD 5 5
WNT10A Odontoonychodermal dysplasia, Tooth agenesis, selective, Schopf-Schulz-Passarge syndrome AD/AR 10 70
YWHAE Distal 17p13.3 microdeletion syndrome, Endometrial stromal sarcoma, 17p13.3 microduplication syndrome, Miller-Dieker syndrome AD/AR 11 42
ZBTB42 Lethal congenital contracture syndrome AR 1 1
ZEB2* Mowat-Wilson syndrome AD 104 247
ZIC2 Holoprosencephaly AD 10 112
ZNF469 Brittle cornea syndrome AR 31 35

*Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (; HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, The list of associated (gene specific) phenotypes are generated from CDG ( or Orphanet ( databases.

Gene Genomic location HG19 HGVS RefSeq RS-number Comment Reference
ADGRG1 Chr16:57673285 c.-435_-421delCAACGGTTGCCAGGG NM_001145774.1
ASPM Chr1:197097820 c.2761-25A>G NM_018136.4 rs199422149
BMP1 Chr8:22058957 c.*241T>C NM_001199.3 rs786205217
CHD7 Chr8:61763035 c.5405-17G>A NM_017780.3 rs794727423
CHRNE Chr17:4806454 c.-96C>T NM_000080.3 rs748144899
COL11A1 Chr1:103491958 c.781-450T>G NM_080629.2 rs587782990
COL1A2 Chr7:94025130 c.70+717A>G NM_000089.3 rs72656354
COL3A1 Chr2:189872183 c.3256-43T>G NM_000090.3 rs587779667
COL5A1 Chr9:137686903 c.2701-25T>G NM_000093.4 rs765079080
COL6A1 Chr21:47409881 c.930+189C>T NM_001848.2
ERCC6 Chr10:50681659 c.2599-26A>G NM_000124.3 rs4253196
ESCO2 Chr8:27650167 c.1354-18G>A NM_001017420.2 rs80359865
FANCC Chr9:98011653 c.-78-2A>G NM_000136.2 rs587779898
GAA Chr17:78078341 c.-32-13T>G NM_000152.3 rs386834236
GAA Chr17:78078351 c.-32-3C>A NM_000152.3
GAA Chr17:78082266 c.1076-22T>G NM_000152.3 rs762260678
GBE1 Chr3:81542963 c.2053-3358_2053-3350delGTGTGGTGGinsTGTTTTTTACATGACAGGT NM_000158.3
GH1 Chr17:61995349 c.291+28G>A NM_000515.3 rs863223306
IFITM5 Chr11:299504 c.-14C>T NM_001025295.2 rs587776916 Explain almost all cases of OI type V PMID 23240094
L1CAM ChrX:153131293 c.2432-19A>C NM_000425.4
LMNA Chr1:156100609 c.513+45T>G NM_170707.3
NF1 Chr17:29577934 c.4110+1802delA NM_001042492.2 rs863224944
NF1 Chr17:29657848 c.5812+332A>G NM_001042492.2 rs863224491
OCRL ChrX:128687279 c.239-4023A>G NM_000276.3
OFD1 ChrX:13773245 c.1130-22_1130-19delAATT NM_003611.2 rs312262865
OFD1 ChrX:13768358 c.935+706A>G NM_003611.2 rs730880283
PAX6 Chr11:31832374 c.-129+2T>A NM_000280.4
PEX7 Chr6:137143759 c.-45C>T NM_000288.3 rs267608252
PNKP Chr19:50364799 c.1387-33_1386+49delCCTCCTCCCCTGACCCC NM_007254.3 rs752902474
PRKAR1A Chr17:66508690 c.-7+1G>A NM_002734.4
PTEN Chr10:89623462 c.-765G>A NM_000314.4
PTEN Chr10:89623365 c.-862G>T NM_000314.4 rs587776675
RAPSN Chr11:47470715 c.-199C>G NM_005055.4
RAPSN Chr11:47470726 c.-210A>G NM_005055.4 rs786200905
RBBP8 Chr18:20581745 c.2287+53T>G NM_002894.2
RYR1 Chr19:39074134 c.14647-1449A>G NM_000540.2 rs193922886
SERPINF1 Chr17:1665408 c.-9+2dupT NM_002615.5 rs398122519
SHOX ChrX:585124 c.-645_-644insGTT NM_000451.3
SLC26A2 Chr5:149340544 c.-26+2T>C NM_000112.3 rs386833492
SMARCB1 Chr22:24176449 c.*82C>T NM_003073.3
TGFB3 Chr14:76425035 c.*495C>T NM_003239.2 rs387906514
TGFB3 Chr14:76447266 c.-30G>A NM_003239.2 rs770828281
TSC2 Chr16:2098067 c.-30+1G>C NM_000548.3 rs587778004
TTC7A Chr2:47249223 c.1510+105T>A NM_020458.2
TXNL4A Chr18:77748603 c.-511_-478del34 NM_006701.2 rs786205699
TXNL4A Chr18:77748580 c.-60-10913_-60-10880del34 NM_006701.2 rs535089924

The strengths of this test include:

  • Blueprint Genetics is one of the few laboratories worldwide with CAP and ISO-15189 accreditation for NGS panels and CLIA certification
  • Superior sequencing quality
  • Careful selection of genes based on current literature, our experience and the most current mutation databases
  • Transparent and easy access to quality and performance data at the patient level that are accessible via our Nucleus portal
  • Transparent and reproducible analytical validation for each panel (see Test performance section; for complete details, see our Analytic Validation)
  • Sequencing and high resolution del/dup analysis available in one test
  • Inclusion of non-coding disease causing variants where clinically indicated (please see individual Panel descriptions)
  • Interpretation of variants following ACMG variant classification guidelines
  • Comprehensive clinical statement co-written by a PhD geneticist and a clinician specialist


This test does not detect the following:

  • Complex inversions
  • Gene conversions
  • Balanced translocations
  • Mitochondrial DNA variants
  • Variants in regulatory or non-coding regions of the gene unless otherwise indicated (please see Non-coding disease causing variants covered by the panel). This mean for instance intronic variants locating deeper than 15 nucleotides from the exon-intron boundary.


This test may not reliably detect the following:

  • Low level mosaicism
  • Stretches of mononucleotide repeats
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments
  • Disorders caused by long repetitive sequences (e.g. trinucleotide repeat expansions)


The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics.

For additional information, please refer to the Test performance section and see our Analytic Validation.

Blueprint Genetics offers a Comprehensive Skeletal / Malformation Syndrome Panel that covers classical genes associated with malformations and skeletal syndromes. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. Average sensitivity and specificity in Blueprint NGS Panels is 99.3% and 99.9% for detecting SNPs. Sensitivity to for indels vary depending on the size of the alteration: 1-10bps (96.0%), 11-20 bps (88.4%) and 21-30 bps (66.7%). The longest detected indel was 46 bps by sequence analysis. Detection limit for Del/Dup (CNV) analysis varies through the genome depending on exon size, sequencing coverage and sequence content. The sensitivity is 71.5% for single exon deletions and duplications and 99% for three exons’ deletions and duplications. We have validated the assays for different starting materials including EDTA-blood, isolated DNA (no FFPE) and saliva that all provide high-quality results. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (, the NHLBI GO Exome Sequencing Project (ESP;, the Exome Aggregation Consortium (ExAC;, ClinVar database of genotype-phenotype associations ( and the Human Gene Mutation Database ( The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (, Polyphen (, and Mutation Taster (

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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ICD & CPT codes

CPT codes

SEQ 81479
DEL/DUP 81479

ICD codes

Commonly used ICD-10 codes when ordering the Comprehensive Skeletal / Malformation Syndrome Panel

ICD-10 Disease
Q89.7 Malformations
Q89.7 Skeletal syndromes

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.


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