Primary Immunodeficiency Panel

Summary
Is a 336 gene panel that includes assessment of non-coding variants.

Is ideal for patients with a clinical suspicion of any type of primary immunodeficiency (PID).

Analysis methods
  • PLUS
Availability
4 weeks
Number of genes
336
Test code
IM0301
Panel tier
Tier 2
CPT Code *
81249, 81222, 81223, 81317, 81319, 81403, 81404 X3, 81405 X3, 81406 X5, 81407, 81408, 81479
* The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Summary

The Blueprint Genetics Primary Immunodeficiency Panel (test code IM0301):

Read about our accreditations, certifications and CE-marked IVD medical devices here.

ICD Codes

Refer to the most current version of ICD-10-CM manual for a complete list of ICD-10 codes.

Sample Requirements

  • Blood (min. 1ml) in an EDTA tube
  • Extracted DNA, min. 2 μg in TE buffer or equivalent
  • Saliva (Please see Sample Requirements for accepted saliva kits)

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

We do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue. In addition, if the patient is affected with a hematological malignancy, DNA extracted from a non-hematological source (e.g. skin fibroblasts) is strongly recommended.

Please note that, in rare cases, mitochondrial genome (mtDNA) variants may not be detectable in blood or saliva in which case DNA extracted from post-mitotic tissue such as skeletal muscle may be a better option.

Read more about our sample requirements here.

Primary immunodeficiencies (PIDs) are a genetically heterogeneous group of diseases. The International Union of Immunological Societies Expert Committee categorizes PIDs into nine different categories: 1) combined immunodeficiencies, 2) combined immunodeficiencies with associated or syndromic features, 3) predominantly antibody deficiencies, 4) diseases of immune dysregulation, 5) congenital defects of phagocyte number, function, or both, 6) defects in intrinsic and innate immunity, 7) autoinflammatory disorders, 8) complement deficiencies and 9) phenocopies of PIDs. Despite a heterogeneous genetic basis, the core symptoms are often very similar complicating the diagnosis. In addition, many PIDs may be included in more than one category. Treatment choice without knowing the specific mutation in the causative gene may therefore be complicated. Also, type and site of and specific organisms causing the infections may help to classify the disease. In addition to immune-related symptoms, many PIDs have non-immune manifestations. The prevalence of individual PIDs have a wide range, but the combined prevalence of all primary immunodeficiencies is reported to be as high as 5-8:10,000. Some recently identified PIDs are extremely rare.

Genes in the Primary Immunodeficiency Panel and their clinical significance

To view complete table content, scroll horizontally.

GeneAssociated phenotypesInheritanceClinVarHGMD
ACDDyskeratosis congenita, autosomal dominant 6, Dyskeratosis congenita, autosomal recessive 7AD/AR28
ACP5Spondyloenchondrodysplasia with immune dysregulationAR1226
ACTB*Baraitser-Winter syndromeAD5560
ADASevere combined immunodeficiency due to adenosine deaminase deficiencyAR4993
ADAM17Inflammatory skin and bowel disease, neonatal 1AR17
ADARDyschromatosis symmetrica hereditaria, Aicardi-Goutières syndromeAD/AR25226
AICDAImmunodeficiency with hyper-IgMAD/AR1450
AIREAutoimmune polyendocrinopathy syndromeAD/AR73134
AK2Reticular dysgenesisAR1417
ALPIInflammatory bowel diseaseAR5
AP3B1Hermansky-Pudlak syndromeAR1434
AP3D1Hermansky-Pudlak syndrome 10AR14
ARHGEF1Idiopathic bronchiectasis, Immunodeficiencies with antibody defectsAR1
ARPC1BPlatelet abnormalities with eosinophilia and immune-mediated inflammatory diseaseAR24
ATMBreast cancer, Ataxia-TelangiectasiaAD/AR10471109
ATP6AP1Immunodeficiency 47XL55
B2MAmyloidosis, systemic visceralAR84
BACH2BACH2-related immunodeficiency and autoimmunity (BRIDA)AD2
BCL10Immunodeficiency 37AR161
BCL11BImmunodeficiency 49AD812
BLMBloom syndromeAR152119
BLNKAgammaglobulinemia 4AR23
BTKHypogammaglobulinemia, Agammaglobulinemia and isolated hormone deficiency, AgammaglobulinemiaXL114908
C17ORF62Chronic granulomatous diseaseAR1
C1QAC1q deficiencyAR27
C1QBC1q deficiencyAR48
C1QCC1q deficiencyAR410
C1SComplement component C1s deficiencyAD/AR410
C2*Complement component 2 deficiencyAR49
C3Hemolytic uremic syndrome, atypical, Complement component 3 deficiency, Macular degeneration, age-relatedAD/AR687
C5#Eculizumab, poor response to, Complement component 5 deficiencyAD/AR618
C6Complement component 6 deficiencyAR812
C7Complement component 7 deficiencyAR1431
C8AComplement component 8 deficiencyAR28
C8BComplement component 8 deficiencyAR78
C9Complement component 9 deficiencyAR79
CARD11B-cell expansion with NFKB and T-cell anergy, ImmunodeficiencyAD/AR129
CARD14PsoriasisAD929
CARD9Candidiasis, familial, 2AR825
CASP10Autoimmune lymphoproliferative syndromeAD57
CASP8Caspase 8 defiencyAR27
CCBE1Hennekam lymphangiectasia-lymphedema syndromeAR613
CD19Immunodeficiency, common variableAR89
CD247ImmunodeficiencyAR84
CD27Lymphoproliferative syndromeAR48
CD3DImmunodeficiencyAR35
CD3EImmunodeficiencyAR47
CD3GImmunodeficiencyAR53
CD4OKT4 epitope deficiencyAR1
CD40Immunodeficiency with Hyper-IgMAR510
CD40LGImmunodeficiency, with hyper-IgMXL35231
CD46*Hemolytic uremic syndrome, atypicalAD/AR581
CD55#Blood group, Cromer systemBG77
CD59CD59 deficiencyAR48
CD70Primary immunodeficiencyAR4
CD79AAgammaglobulinemia 3AR37
CD79BAgammaglobulinemia 6AR23
CD81Immunodeficiency, common variable, 6AR11
CD8ACD8 deficiencyAR11
CDC42*Takenouchi-Kosaki syndrome, Noonan-syndrome like phenotypeAD119
CDCA7Immunodeficiency-centromeric instability-facial anomalies syndrome 3AR46
CDK9AR1
CEBPESpecific granule deficiency 1AR34
CECR1Polyarteritis nodosa, ADA2 deficiencyAR1550
CFBComplement factor B deficiency, Hemolytic uremic syndrome, atypicalAD/AR226
CFDComplement factor D deficiencyAR23
CFH*Hemolytic uremic syndrome, atypical, Complement factor H deficiency, Basal laminar drusenAD/AR18305
CFIHemolytic uremic syndrome, atypical, Complement factor I deficiencyAD/AR10143
CFPProperdin deficiencyXL517
CFTRCystic fibrosis, Congenital bilateral absence of the vas deferensAD/AR5181803
CHD7Isolated gonadotropin-releasing hormone deficiency, CHARGE syndromeAD276860
CIITABare lymphocyte syndromeAR915
CLCN7OsteopetrosisAD/AR1598
CLPB3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia (MEGCANN)AD/AR2625
COG6Congenital disorder of glycosylation, Shaheen syndromeAR109
COLEC113MC syndromeAR613
COPAAutoimmune interstitial lung, joint, and kidney diseaseAD66
CORO1A#*ImmunodeficiencyAR416
CR2Common variable immunodeficiencyAR216
CSF2RA#*Surfactant metabolism dysfunction, pulmonaryXL217
CSF2RBSurfactant metabolism dysfunction, pulmonary, 5AR26
CSF3RNeutrophilia, hereditaryAD/AR1313
CTC1Cerebroretinal microangiopathy with calcifications and cystsAR2133
CTLA4Autoimmune lymphoproliferative syndrome, type VAD1134
CTPS1Immunodeficiency 24AR11
CTSCPeriodontitis, juvenile, Haim-Munk syndrome, Papillon-Lefevre syndromeAR1992
CXCR4Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndromeAD515
CYBAChronic granulomatous diseaseAR1371
CYBBChronic granulomatous disease, ImmunodeficiencyXL69780
CYP27A1Cerebrotendinous xanthomatosisAR69110
DBR1ImmunodeficiencyAR1
DCLRE1C*Omenn syndrome, Severe combined immunodeficiency with sensitivity to ionizing radiationAR1889
DDX58Singleton-Merten syndromeAD43
DGAT1DiarrheaAR711
DGKENephrotic syndromeAR1738
DIAPH1Seizures, cortical blindness, and microcephaly syndrome (SCBMS), Deafness, autosomal dominant 1AD/AR1015
DKC1Hoyeraal-Hreidarsson syndrome, Dyskeratosis congenitaXL4874
DNAJC21Bone marrow failure syndrome 3AR511
DNASE1L3Systemic lupus erythematosus 16AR13
DNASE2Autoinflammatory-pancytopenia syndromeAR2
DNMT3BImmunodeficiency-centromeric instability-facial anomalies syndromeAR1447
DOCK2ImmunodeficiencyAR76
DOCK8Hyper-IgE recurrent infection syndrome, Mental retardation, autosomal dominant 2AR54168
DSG1Severe dermatitis, multiple allergies, and metabolic wasting syndrome (SAM syndrome), Keratosis palmoplantaris striata IAD/AR1331
EFL1*Shwachman-Diamond syndrome32
ELANENeutropeniaAD43217
EPG5Vici syndromeAR3666
ERCC6L2Bone marrow failure syndrome 2AR49
EXTL3Immunoskeletal dysplasia with neurodevelopmental abnormalities (ISDNA)AR48
FADDInfections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovascular malformationsAR21
FANCAFanconi anemiaAR191677
FASAutoimmune lymphoproliferative syndromeAD/AR31133
FASLGAutoimmune lymphoproliferative syndrome, type IBAD/AR210
FAT4Van Maldergem syndrome 2AR1333
FCGR3A*Immunodeficiency 20AR1
FCHO1Combined immunodeficiencyAR
FERMT3Leukocyte adhesion deficiencyAR814
FOXN1T-cell immunodeficiency, congenital alopecia, and nail dystrophyAD/AR66
FOXP3Immunodysregulation, polyendocrinopathy, and enteropathyXL2893
G6PCGlycogen storage diseaseAR46117
G6PC3Neutropenia, severe congenital, Dursun syndromeAR1137
G6PDGlucose-6-phosphate dehydrogenase deficiencyXL45226
GATA2Myelodysplastic syndrome, Chronic neutropenia associated with monocytopenia, evolving to myelodysplasia and acute myeloid leukemia, Acute myeloid leukemia, Emberger syndrome, ImmunodeficiencyAD30142
GFI1Neutropenia, severe congenital, 2 autosomal dominant, Neutropenia, nonimmune chronic idiopathic, of adultsAD26
GINS1ImmunodeficiencyAR44
GUCY2CDiarrhea, Meconium ileusAD/AR710
HAVCR2AR
HAX1Neutropenia, severe congenitalAR1121
HELLSImmunodeficiency-centromeric instability-facial anomalies syndrome 4AR66
HMOX1Heme oxygenase 1 deficiencyAR25
HYOU1Combined immunodeficiencyAR2
ICOSImmunodeficiency, common variable, 1AR34
IFIH1Singleton-Merten syndrome, Aicardi-Goutieres syndrome 7AD/AR1419
IFNAR2Immunodeficiency 45AR12
IFNGR1ImmunodeficiencyAD/AR1642
IFNGR2ImmunodeficiencyAR418
IGLL1*AgammaglobulinemiaAR23
IKBKBImmunodeficiency 15AR27
IKZF1Immunodeficiency, common variable, 13AD1035
IL10Inflammatory bowel diseaseAD/AR15
IL10RAInflammatory bowel diseaseAR443
IL10RBInflammatory bowel diseaseAR219
IL12BImmunodeficiency 28, Immunodeficiency 29AR413
IL12RB1#ImmunodeficiencyAR1382
IL17RAImmunodeficiency 51AR817
IL17RCCandiasis, familial, 9AR34
IL1RNOsteomyelitis, sterile multifocal, with periostitis and pustulosisAR612
IL21Immunodeficiency, common variable, 11AR11
IL21RImmunodeficiency, primary, autosomal recessive, IL21R-relatedAD/AR39
IL23RPrimary immunodeficiencyAR1
IL2RAInterleukin 2 receptor, alpha, deficiencyAR66
IL2RBAutoinflammatory-pancytopenia syndromeAR
IL2RGCombined immunodeficiencyXL54243
IL36RNPustular psoriasis, generalizedAR626
IL6RAutoinflammatory-pancytopenia syndromeAR1
IL6ST*Autoinflammatory-pancytopenia syndromeAD/AR
IL7Interleukin 7 deficiency, Generalized verrucosis, HPV susceptibilityAD/AR
IL7RSevere combined immunodeficiency, , T-cell negative, B-cell positive, NK cell positiveAR2348
IRAK4IRAK4 deficiency, Invasive pneumococcal disease, recurrent, isolated, 1AR1229
IRF2BP2Immunodeficiency, common variable, 14AD12
IRF4Skin/hair/eye pigmentation, variation in, 8AD1
IRF7Immunodeficiency 39AR22
IRF8Immunodeficiency 32A (CD11C-positive/CD1C-positive dendritic cell deficiency), Immunodeficiency 32B (monocyte and dendritic cell deficiency)AD/AR48
ISG15Immunodeficiency, with basal ganglia calcificationAR33
ITGB2Leukocyte adhesion deficiencyAR33118
ITKLymphoproliferative syndromeAR411
JAGN1Neutropenia, severe congenitalAR88
JAK1Primary immunodeficiencyAD/AR46
JAK3Severe combined immunodeficiency, , T cell-negative, B cell-positive, natural killer cell-negativeAR3066
KRAS*Noonan syndrome, Cardiofaciocutaneous syndromeAD6335
LAMTOR2Immunodeficiency due to defect in MAPBP-interacting proteinAR11
LATImmunodeficiency 52AR218
LCKImmunodeficiencyAR23
LIG1Autoinflammatory-pancytopenia syndromeAR3
LIG4Severe combined immunodeficiency with sensitivity to ionizing radiation, LIG4 syndromeAR1836
LPIN2Majeed syndromeAR1214
LRBACommon variable immunodeficiencyAR2364
LYSTChediak-Higashi syndromeAR5097
MAGT1Immunodeficiency, with magnesium defect, Epstein-Barr virus infection and neoplasia, Mental retardation, X-linked 95XL814
MALT1ImmunodeficiencyAR35
MAP3K14Primary immunodeficiency with multifaceted aberrant lymphoid immunityAR12
MASP13MC syndromeAR1122
MEFVFamilial Mediterranean feverAD/AR29182
MKL1Primary immunodeficiencyAR4
MOGSCongenital disorder of glycosylationAR78
MRE11AAtaxia-telangiectasia-like disorder-1AR5756
MSN*Immunodeficiency 50XL22
MTHFD1Severe combined immunodeficiencyAR911
MVKMevalonic aciduria, Hyper-IgD syndrome, Porokeratosis 3, multiple typesAD/AR35181
MYD88MYD88 deficiencyAR55
MYO5AGriscelli syndromeAR79
NBNBreast cancer, Nijmegen breakage syndromeAD/AR18897
NCF1#*Chronic granulomatous diseaseAR1844
NCF2Chronic granulomatous diseaseAR1972
NCF4Granulomatous diseaseAR45
NCSTNAcne inversa, familial 1AD730
NFE2L2116
NFKB1Common variable immunodeficiencyAD817
NFKB2Common variable immunodeficiencyAD611
NFKBIAEctodermal dysplasia, anhidrotic, with T-cell immunodeficiencyAD511
NHEJ1Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiationAR1516
NHP2Dyskeratosis congenitaAR53
NLRC4Autoinflammation with infantile enterocolitis (AIFEC), Familial cold autoinflammatory syndrome 4AD68
NLRP1Palmoplantar carcinoma, multiple self-healing, Autoinflammation with arthritis and dyskeratosisAD/AR515
NLRP12Familial cold autoinflammatory syndromeAD1212
NLRP3Neonatal onset multisystem inflammatory disease (NOMID), Muckle-Wells syndrome, Chronic infantile neurologic cutaneous articular (CINCA) syndrome, Familial cold-induced autoinflammatory syndrome 1, DeafnessAD20136
NOD2Blau syndrome, Sarcoidosis, early-onsetAD1270
NOP10Dyskeratosis congenitaAR11
NRASNoonan syndromeAD3114
NSMCE3Lung disease, immunodeficiency, and chromosome breakage syndrome (LICS)AR22
OBFC122
OFD1Simpson-Golabi-Behmel syndrome, Retinitis pigmentosa, Orofaciodigital syndrome, Joubert syndromeXL153160
ORAI1Immunodeficiency, Myopathy, tubular aggregate, 2AD/AR913
OTULINAutoinflammation, panniculitis, and dermatosis syndrome (AIPDS)AR83
PARN*Pulmonary fibrosis and/or bone marrow failure, Dyskeratosis congenitaAD/AR1529
PEPDProlidase deficiencyAR1231
PGM3Immunodeficiency 23AR1415
PIGA*Multiple congenital anomalies-hypotonia-seizures syndromeXL2427
PIK3CD*ImmunodeficiencyAD612
PIK3R1Agammaglobulinemia, SHORT syndromeAD/AR3324
PLCG2Familial cold autoinflammatory syndrome 3 (PLAID), Autoinflammation, antibody deficiency, and immune dysregulation syndrome (APLAID)AD713
PMS2*Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposisAD/AR319342
PNPPurine nucleoside phosphorylase deficiencyAR1133
POLA1Pigmentary disorder, reticulate, with systemic manifestations, X-linked, Neurodevelopmental disorder21
POLD1Colorectal cancer, Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, Idiopathic bronchiectasis, ImmunodeficiencyAD/AR331
POLEColorectal cancer, Facial dysmorphism, immunodeficiency, livedo, and short stature syndrome (FILS syndrome)AD/AR870
POLE2Combined immunodeficiencyAR3
POMPKeratosis linearis with ichthyosis congenita and sclerosing keratodermaAR54
PRF1Lymphoma, non-Hodgkin, Aplastic anemia, adult-onset, Hemophagocytic lymphohistiocytosisAR24183
PRG4Camptodactyly-arthropathy-coxa vara-pericarditis syndromeAR635
PRKCDAutoimmune lymphoproliferative syndrome type IIIAR46
PRKDCImmunodeficiencyAR69
PSENENAcne inversa, familial, 2AD717
PSMB444
PSMB8Nakajo-Nishimura syndrome, Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome, Autoinflammation, lipodystrophy, and dermatosis syndrome, Joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy syndromeAR59
PSTPIP1Pyogenic sterile arthritis, pyoderma gangrenosum, and acneAD529
PTPRCSevere combined immunodeficiency, , T-cell negative, B-cell positive, NK cell positiveAR45
RAB27AGriscelli syndrome, Elejalde syndromeAR1854
RAC2Neutrophil immunodeficiency syndromeAD23
RAG1Omenn syndrome, Alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity, T cell-negative, B cell-negative, natural killer cell-positive severe combined immunodeficiency, Combined cellular and humoral immune defects with granulomasAR47184
RAG2Omenn syndrome, Combined cellular and humoral immune defects with granulomasAR2879
RANBP2*Encephalopathy, acute, infection-induced, 3, susceptibility toAD416
RASGRP1Primary immunodeficiencyAR13
RBCK1Polyglucosan body myopathyAR1114
RECQL4Baller-Gerold syndrome, RAPADILINO syndrome, Rothmund-Thomson syndromeAR82114
RELA*Autoimmune lymphoproliferative syndromeAD13
RELBImmunodeficiency 5311
RFX5Bare lymphocyte syndromeAR410
RFXANKMHC class II deficiencyAR816
RFXAPBare lymphocyte syndromeAR69
RHOHT-cell immunodeficiency with epidermodysplasia verruciformisAD/AR1
RIPK1Autoinflammatory-pancytopenia syndromeAD/AR31
RLTPRCombined immunodeficiencyAR118
RMRPCartilage-hair hypoplasia, Metaphyseal dysplasia without hypotrichosis, Anauxetic dysplasiaAR87123
RNASEH2AAicardi-Goutières syndromeAR1321
RNASEH2BAicardi-Goutières syndromeAR1641
RNASEH2CAicardi-Goutières syndromeAR614
RNF168RIDDLE syndromeAR45
RNF31HOIP and LUBAC deficiencyAR1
RNU4ATACRoifman syndrome, Microcephalic osteodysplastic primordial dwarfism type 1, Microcephalic osteodysplastic primordial dwarfism type 3AR1524
RORCImmunodeficiency 42AR33
RPSAAsplenia, isolated congenitalAD78
RTEL1Pulmonary fibrosis and/or bone marrow failure, Dyskeratosis congenitaAD/AR5851
SAMD9Mirage syndrome, Tumoral calcinosis, normophosphatemicAD/AR1027
SAMD9LAtaxia-pancytopenia syndromeAD416
SAMHD1Aicardi-Goutières syndrome, Chilblain lupus 2AD/AR2556
SBDS*Aplastic anemia, Shwachman-Diamond syndrome, Severe spondylometaphyseal dysplasiaAR1990
SEC61A1Hyperuricemic nephropathy, familial juvenile 4AD44
SERPING1Angioedema, Complement component 4, partial deficiency ofAD/AR34563
SH2D1ALymphoproliferative syndromeXL21129
SLC29A3Histiocytosis-lymphadenopathy plus syndrome, DysosteosclerosisAR1725
SLC35C1Congenital disorder of glycosylation, Leukocyte adhesion deficiencyAR67
SLC37A4Glycogen storage diseaseAD/AR49113
SLC39A7AgammaglobulinemiaAR
SLC46A1Folate malabsorptionAR1723
SLC7A7Lysinuric protein intoleranceAR5567
SMARCAL1Schimke immunoosseous dysplasiaAR2088
SMARCD2Specific granule defiency 2AR31
SP110Hepatic venoocclusive disease with immunodeficiencyAR88
SPINK5Netherton syndromeAR2985
SPPL2AAutoinflammatory-pancytopenia syndromeAR1
SRP54Shwachman-Diamond syndromeAD3
SRP72*Bone marrow failure syndrome 1AD25
STAT1ImmunodeficiencyAD/AR39122
STAT2ImmunodeficiencyAR36
STAT3Hyper-IgE recurrent infection syndrome, Autoimmune disease, multisystem, infantile onsetAD47152
STAT5B*Growth hormone insensitivity with immunodeficiencyAD/AR913
STIM1Stormorken syndrome, Immunodeficiency, Myopathy, tubular aggregate 1AD/AR1324
STK4T-cell immunodeficiency syndrome, recurrent infections, autoimmunity,AR37
STX11Hemophagocytic lymphohistiocytosis, familialAR822
STXBP2Hemophagocytic lymphohistiocytosis, familialAR1277
TAP1Bare lymphocyte syndromeAR17
TAP2Bare lymphocyte syndromeAR48
TAPBPBare lymphocyte syndromeAR12
TAZ3-Methylglutaconic aciduria, (Barth syndrome)XL45158
TBX1Conotruncal anomaly face syndromeAD1772
TCF3Agammaglobulinemia 8, autosomal dominantAD15
TCN2Transcobalamin II deficiencyAR935
TERCAplastic anemia, Pulmonary fibrosis and/or bone marrow failure, telomere-related, Dyskeratosis congenitaAD4273
TERTAplastic anemia, Pulmonary fibrosis and/or bone marrow failure, telomere-related, Dyskeratosis congenitaAD/AR48156
TFRCImmunodeficiency 46AR82
TGFB1Diaphyseal dysplasia Camurati-EngelmannAD1523
THBDThrombophilia due to thrombomodulin defect, Hemolytic uremic syndrome, atypicalAD528
TINF2Revesz syndrome, Dyskeratosis congenitaAD2542
TLR3Herpes simplex encephalitis, susceptibility to, 2AD/AR14
TMC6Epidermodysplasia verruciformisAR87
TMC8Epidermodysplasia verruciformisAR39
TMEM173STING-associated vasculopathy, infantile-onsent (SAVI)AD/AR410
TNFAIP3Autoinflammatory syndrome, familial, Behcet-likeAD823
TNFRSF13BCommon variable immunodeficiency, Immunoglobulin A deficiencyAD/AR748
TNFRSF1A#Periodic fever (TNF receptor-associated periodic syndrome)AD19106
TNFRSF4ImmunodeficiencyAR11
TNFRSF9
TRAF3IP2Candidiasis, familial 8AR13
TREX1Vasculopathy, retinal, with cerebral leukodystrophy, Chilblain lupus, Aicardi-Goutières syndromeAD/AR3071
TRNT1Retinitis pigmentosa and erythrocytic microcytosis, Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delayAR1326
TTC37Trichohepatoenteric syndrome, Autoinflammatory-pancytopenia syndromeAR1264
TTC7AGastrointestinal defects and immunodeficiency syndromeAR2146
TYK2ImmunodeficiencyAR99
UBA1Spinal muscular atrophy, infantileXL35
UNC119Immunodeficiency, Cone-rod dystrophy 2AD15
UNC13DHemophagocytic lymphohistiocytosis, familialAR22192
UNC93B1*Herpes simplex encephalitis, susceptibility to, 1AR2
UNGImmunodeficiency with hyper-IgM, type 5AR67
USB1Poikiloderma with neutropeniaAR2422
USP18#*Pseudo-TORCH syndrome 2AR401
VPS13BCohen syndromeAR351203
VPS45#Neutropenia, severe congenital, 5, autosomal recessiveAR34
WASNeutropenia, severe congenital, Thrombocytopenia, Wiskott-Aldrich syndromeXL57439
WDR1AR8
WIPF1Wiskott-Aldrich syndrome 2AR23
WRAP53Dyskeratosis congenitaAR76
XIAP*Lymphoproliferative syndromeXL1496
ZAP70Selective T-cell defectAR1529
ZBTB24Immunodeficiency-Centromeric Instability-Facial Anomalies 2AR717
ZNF341*AR5
#

The gene has suboptimal coverage (means <90% of the gene’s target nucleotides are covered at >20x with mapping quality score (MQ>20) reads), and/or the gene has exons listed under Test limitations section that are not included in the panel as they are not sufficiently covered with high quality sequence reads.

*

Some, or all, of the gene is duplicated in the genome. Read more.

The sensitivity to detect variants may be limited in genes marked with an asterisk (*) or number sign (#). Due to possible limitations these genes may not be available as single gene tests.

Gene refers to the HGNC approved gene symbol; Inheritance refers to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR), mitochondrial (mi), X-linked (XL), X-linked dominant (XLD) and X-linked recessive (XLR); ClinVar refers to the number of variants in the gene classified as pathogenic or likely pathogenic in this database (ClinVar); HGMD refers to the 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 CGD or Mitomap databases.

Non-coding variants covered by Primary Immunodeficiency Panel

To view complete table content, scroll horizontally.

GeneGenomic location HG19HGVSRefSeqRS-number
ADAChr20:43248503c.1079-15T>ANM_000022.2rs387906268
ADAChr20:43249076c.976-34G>ANM_000022.2
ATMChr11:108093770c.-174A>GNM_000051.3
ATMChr11:108094508c.-31+595G>ANM_000051.3
ATMChr11:108098321c.-30-1G>TNM_000051.3rs869312754
ATMChr11:108138753c.2639-384A>GNM_000051.3
ATMChr11:108141209c.2839-579_2839-576delAAGTNM_000051.3
ATMChr11:108151710c.3403-12T>ANM_000051.3rs201370733
ATMChr11:108158168c.3994-159A>GNM_000051.3rs864622543
ATMChr11:108164028c.4612-12A>GNM_000051.3
ATMChr11:108179837c.5763-1050A>GNM_000051.3rs774925473
ATMChr11:108214779c.8418+681A>GNM_000051.3rs748635985
BTKChrX:100609705c.1567-23A>C/GNM_000061.2
BTKChrX:100609705c.1567-23A>GNM_000061.2
BTKChrX:100609705c.1567-23A>CNM_000061.2
BTKChrX:100612468c.1177+28_1177+29insAGAAAAAAGGTNM_000061.2
BTKChrX:100613695c.895-11C>ANM_000061.2
BTKChrX:100625094c.310-28_310-27delGCinsTGNM_000061.2
BTKChrX:100629415c.240+109C>ANM_000061.2
BTKChrX:100629416c.240+108T>GNM_000061.2
BTKChrX:100629827c.142-205A>GNM_000061.2
BTKChrX:100630121c.141+11C>TNM_000061.2rs138411530
BTKChrX:100641044c.-31+6T>GNM_000061.2
BTKChrX:100641045c.-31+5G>A/C/TNM_000061.2
BTKChrX:100641045c.-31+5G>ANM_000061.2
BTKChrX:100641045c.-31+5G>TNM_000061.2rs1131691354
BTKChrX:100641045c.-31+5G>CNM_000061.2
BTKChrX:100641049c.-31+1G>A/CNM_000061.2
BTKChrX:100641049c.-31+1G>ANM_000061.2
BTKChrX:100641049c.-31+1G>CNM_000061.2
BTKChrX:100641050c.-31G>ANM_000061.2
BTKChrX:100641212c.-193A>GNM_000061.2
C1QBChr1:22985931c.-17-2A>CNM_000491.3
C7Chr5:40931143c.63-23T>ANM_000587.2rs772462732
CD40LGChrX:135736498c.289-32_289-25delAAAATGACNM_000074.2
CD40LGChrX:135736517c.289-15T>ANM_000074.2
CD40LGChrX:135737600c.347-915A>TNM_000074.2
CD46Chr1:207930564c.286+27delTNM_002389.4rs771669828
CECR1Chr22:17664763c.1082-1113delANM_017424.2
CFTRChr7:117119654c.-495C>TNM_000492.3rs397507565
CFTRChr7:117119797NM_000492.3
CFTRChr7:117119900c.-249G>CNM_000492.3
CFTRChr7:117119984c.-165G>ANM_000492.3rs145483167
CFTRChr7:117120064c.-85C>GNM_000492.3
CFTRChr7:117120115c.-34C>TNM_000492.3rs756314710
CFTRChr7:117120325c.53+124T>CNM_000492.3
CFTRChr7:117179040c.870-1113_870-1110delGAATNM_000492.3rs397508809
CFTRChr7:117182041c.1117-26_1117-25delATNM_000492.3rs397508159
CFTRChr7:117199500c.1393-18G>ANM_000492.3rs397508199
CFTRChr7:117218381c.1585-9412A>GNM_000492.3rs397508229
CFTRChr7:117227774c.1585-19T>CNM_000492.3rs778457306
CFTRChr7:117227921c.1679+34G>TNM_000492.3rs767901668
CFTRChr7:117229521c.1680-886A>GNM_000492.3rs397508266
CFTRChr7:117229524c.1680-883A>GNM_000492.3
CFTRChr7:117229530c.1680-877G>TNM_000492.3rs397508261
CFTRChr7:117243855c.2908+19G>CNM_000492.3rs370683572
CFTRChr7:117246713c.2909-15T>GNM_000492.3rs397508455
CFTRChr7:117246840c.2988+33G>TNM_000492.3
CFTRChr7:117251609c.3140-26A>GNM_000492.3rs76151804
CFTRChr7:117251619c.3140-16T>ANM_000492.3rs767232138
CFTRChr7:117251624c.3140-11A>GNM_000492.3
CFTRChr7:117266272c.3469-1304C>GNM_000492.3
CFTRChr7:117267864c.3717+40A>GNM_000492.3rs397508595
CFTRChr7:117280015c.3718-2477C>TNM_000492.3rs75039782
CFTRChr7:117282680c.3873+33A>GNM_000492.3rs397508622
CFTRChr7:117288374c.3874-4522A>GNM_000492.3
CFTRChr7:117308395c.*1233T>ANM_000492.3
CHD7Chr8:61734568c.2836-15C>GNM_017780.3
CHD7Chr8:61757794c.5051-15T>ANM_017780.3
CHD7Chr8:61763034c.5405-18C>ANM_017780.3rs199981784
CHD7Chr8:61763035c.5405-17G>ANM_017780.3rs794727423
CHD7Chr8:61763039c.5405-13G>ANM_017780.3rs1131690787
CLCN7Chr16:1506057c.916+57A>TNM_001287.5
CLCN7Chr16:1507356c.739-18G>ANM_001287.5rs371893553
COG6Chr13:40273614c.1167-24A>GNM_020751.2rs730882236
CTSCChr11:88070895c.-55C>ANM_001814.4rs766114323
CYBAChr16:88712620c.288-15C>GNM_000101.3
CYBBChrX:37639262c.-69A>CNM_000397.3
CYBBChrX:37639262NM_000397.3
CYBBChrX:37639264c.-67T>CNM_000397.3
CYBBChrX:37639266c.-65C>TNM_000397.3
CYBBChrX:37639267c.-64C>TNM_000397.3
CYBBChrX:37641327c.46-14_46-11delTTCTinsGAANM_000397.3
CYBBChrX:37641330c.46-11T>GNM_000397.3
CYBBChrX:37642713c.142-28_142-12delACTCTGCTCCCTTTCCCNM_000397.3
CYBBChrX:37642731c.142-12delCinsACCTCTTCTAGNM_000397.3
CYBBChrX:37654041c.483+978G>TNM_000397.3
CYBBChrX:37656474c.674+1080A>GNM_000397.3
CYBBChrX:37656731c.674+1337T>GNM_000397.3
CYBBChrX:37657051c.675-1157A>GNM_000397.3
CYBBChrX:37664248c.1152-11T>GNM_000397.3
DGKEChr17:54925466c.888+40A>GNM_003647.2
DKC1ChrX:153991099c.-142C>GNM_001363.3rs199422241
DKC1ChrX:153991100c.-141C>GNM_001363.3
DKC1ChrX:153993704c.85-15T>CNM_001363.3
DNMT3BChr20:31395557c.2421-11G>ANM_006892.3rs547940069
DOCK8Chr9:317025c.742-18C>GNM_203447.3rs112373444
DOCK8Chr9:317028c.742-15T>GNM_203447.3rs111627162
DOCK8Chr9:368196c.1797+61A>CNM_203447.3rs786205596
FANCAChr16:89805127c.4261-19_4261-12delACCTGCTCNM_000135.3
FANCAChr16:89816056c.3239+82T>GNM_000135.2
FANCAChr16:89818822c.2982-192A>GNM_000135.2
FANCAChr16:89831215c.2778+83C>GNM_000135.2rs750997715
FANCAChr16:89836111c.2504+134A>GNM_000135.2
FANCAChr16:89836805c.2223-138A>GNM_000135.2
FANCAChr16:89849346c.1567-20A>GNM_000135.2rs775154397
FANCAChr16:89864654c.893+920C>ANM_000135.2
FASChr10:90770494c.506-16A>GNM_000043.4
FASLGChr1:172628081c.-261T>CNM_000639.1
FOXP3ChrX:49106917c.*878A>GNM_014009.3
FOXP3ChrX:49106919c.*876A>GNM_014009.3
FOXP3ChrX:49121118c.-23+5G>ANM_014009.3
FOXP3ChrX:49121121c.-23+2T>GNM_014009.3
FOXP3ChrX:49121122c.-23+1G>ANM_014009.3
FOXP3ChrX:49121122c.-23+1G>TNM_014009.3
G6PCChr17:41059684c.446+39G>ANM_000151.3
G6PCChr17:41059687c.446+42G>ANM_000151.3
GATA2Chr3:128202131c.1017+572C>TNM_032638.4
GATA2Chr3:128202162c.1017+513_1017+540delGGAGTTTCCTATCCGGACATCTGCAGCCNM_032638.4
GATA2Chr3:128202171c.1017+532T>ANM_032638.4
GINS1Chr20:25388397c.-60A>GNM_021067.3
GINS1Chr20:25388409c.-48C>GNM_021067.3
IL10RBChr21:34668714c.*52C>TNM_000628.4
IL2RGChrX:70327277c.*307_*308delAANM_000206.2
IL2RGChrX:70327278c.*308A>GNM_000206.2
IL2RGChrX:70330553c.270-15A>GNM_000206.2
IL2RGChrX:70331494c.-105C>TNM_000206.2
IL7RChr5:35867853c.379+288G>ANM_002185.3
IRAK4Chr12:44178047c.1188+520A>GNM_016123.3
ITGB2Chr21:46320404c.742-14C>ANM_000211.3rs183204825
ITGB2Chr21:46321660c.500-12T>GNM_000211.3
JAK3Chr19:17943239c.2680+89G>ANM_000215.3
JAK3Chr19:17946035c.1915-11G>ANM_000215.3
LAMTOR2Chr1:156028185c.*23C>ANM_014017.3
MEFVChr16:3306599c.-12C>GNM_000243.2rs104895148
MEFVChr16:3306969c.-382C>GNM_000243.2
MVKChr12:110029032c.769-7dupTNM_000431.2rs104895348
OFD1ChrX:13768358c.935+706A>GNM_003611.2rs730880283
OFD1ChrX:13773245c.1130-22_1130-19delAATTNM_003611.2rs312262865
OFD1ChrX:13773249c.1130-20_1130-16delTTGGTNM_003611.2
PARNChr16:14724045c.-165+2C>TNM_001134477.2
PMS2Chr7:6027263c.1145-31_1145-13delCTGACCCTCTTCTCCGTCCNM_000535.5rs751973268
PMS2Chr7:6048599c.23+21_23+28delTCCGGTGTNM_000535.5
PNPChr14:20942914c.286-18G>ANM_000270.3
POLA1ChrX:24744696c.1375-354A>GNM_016937.3rs869312979
POLEChr12:133249181c.1686+32C>GNM_006231.2rs762985435
POMPChr13:29233225c.-95delCNM_015932.5rs112368783
PSENENChr19:36236501c.-192_-190delAGANM_172341.2rs554724520
RAG2Chr11:36619652c.-28G>CNM_000536.3
RFXANKChr19:19307761c.188-11C>TNM_003721.3rs201545133
RMRPChr9:35658026NR_003051.3rs781730798
RMRPChr9:35658026NR_003051.3
RMRPChr9:35658026NR_003051.3
RMRPChr9:35658026NR_003051.3
RMRPChr9:35658027NR_003051.3
RMRPChr9:35658027NR_003051.3
RMRPChr9:35658027NR_003051.3
RMRPChr9:35658027NR_003051.3rs727502775
RMRPChr9:35658027NR_003051.3
RMRPChr9:35658028NR_003051.3
RMRPChr9:35658028NR_003051.3
RMRPChr9:35658029NR_003051.3
RMRPChr9:35658029NR_003051.3
RMRPChr9:35658032NR_003051.3
RNASEH2BChr13:51501530c.65-13G>ANM_024570.3
RNASEH2BChr13:51519550c.511-13G>ANM_024570.3
RPSAChr3:39448260c.-34+5G>CNM_002295.4
SERPING1Chr11:57365055c.-163C>TNM_000062.2
SERPING1Chr11:57365057c.-161A>GNM_000062.2
SERPING1Chr11:57365118c.-100C>GNM_000062.2rs578018379
SERPING1Chr11:57365720c.-22-2A>C/GNM_000062.2
SERPING1Chr11:57365720c.-22-2A>CNM_000062.2
SERPING1Chr11:57365720c.-22-2A>GNM_000062.2
SERPING1Chr11:57365721c.-22-1G>ANM_000062.2
SERPING1Chr11:57373471c.686-12A>GNM_000062.2
SERPING1Chr11:57373867c.890-14C>GNM_000062.2
SERPING1Chr11:57381788c.1250-13G>ANM_000062.2
SH2D1AChrX:123499593c.138-17_138-11delAGTTTATNM_002351.4
SLC29A3Chr10:73122778c.*413G>ANM_018344.5
SPINK5Chr5:147465956c.283-12T>ANM_006846.3
SPINK5Chr5:147484503c.1431-12G>ANM_006846.3rs368134354
SPINK5Chr5:147491511c.1820+53G>ANM_006846.3rs754599628
STX11Chr6:144508713c.*85_*86insTNM_003764.3
STXBP2Chr19:7705761c.326-23_326-16delGCCCCACTNM_006949.3
TAZChrX:153641699n.694+4G>ANR_024048.1
TAZChrX:153649161c.778-63_778-51delCTCCCAGGGCACCNM_000116.3rs782249471
TBX1Chr22:19743578c.-777C>TNM_080647.1
TBX1Chr22:19743735c.-620A>CNM_080647.1rs536892777
TCN2Chr22:31011112c.581-176A>TNM_000355.3
TCN2Chr22:31011112c.581-176A>GNM_000355.3rs372866837
TERCChr3:169482870n.-22C>TNR_001566.1
TERCChr3:169482906NR_001566.1
TERCChr3:169482948n.-100C>GNR_001566.1rs199422256
TERCChr3:169483086NR_001566.1rs199422255
TERTChr5:1271334c.2383-15C>TNM_198253.2rs574645600
TERTChr5:1295161c.-57A>CNM_198253.2
THBDChr20:23030319NM_000361.2
THBDChr20:23030443c.-302C>ANM_000361.2
TRNT1Chr3:3188088c.609-26T>CNM_182916.2
TTC7AChr2:47249223c.1510+105T>ANM_020458.2
UNC13DChr17:73826245c.2831-13G>ANM_199242.2
UNC13DChr17:73827442c.2448-13G>ANM_199242.2rs753762300
UNC13DChr17:73839907c.118-307G>ANM_199242.2
UNC13DChr17:73839908c.118-308C>TNM_199242.2
WASChrX:48547690c.1339-19_1339-11delTGATCCCTGinsATCTGCAGACCNM_000377.2
ZAP70Chr2:98349927c.838-80G>ANM_001079.3rs113994173
ZAP70Chr2:98354447c.1624-11G>ANM_001079.3rs730880318

Test Strengths

The strengths of this test include:

  • CAP accredited laboratory
  • CLIA-certified personnel performing clinical testing in a CLIA-certified laboratory
  • Powerful sequencing technologies, advanced target enrichment methods and precision bioinformatics pipelines ensure superior analytical performance
  • Careful construction of clinically effective and scientifically justified gene panels
  • Some of the panels include the whole mitochondrial genome (please see the Panel Content section)
  • Our Nucleus online portal providing transparent and easy access to quality and performance data at the patient level
  • ~2,000 non-coding disease causing variants in our clinical grade NGS assay for panels (please see ‘Non-coding disease causing variants covered by this panel’ in the Panel Content section)
  • Our rigorous variant classification scheme
  • Our systematic clinical interpretation workflow using proprietary software enabling accurate and traceable processing of NGS data
  • Our comprehensive clinical statements

Test Limitations

The following exons are not included in the panel as they are not sufficiently covered with high quality sequence reads: *C5* (NM_001317164:21), *CD55* (NM_001114752:10;NM_001300903:10), *CORO1A* (NM_007074:11), *CSF2RA* (NM_001161530:9), *IL12RB1* (NM_153701:10), *NCF1* (NM_000265:1,5,8,9,11), *TNFRSF1A* (NM_001346092:6), *USP18* (NM_017414:11), *VPS45* (NM_001279353:13). Genes with suboptimal coverage in our assay are marked with number sign (#) and genes with partial, or whole gene, segmental duplications in the human genome are marked with an asterisk (*) if they overlap with the UCSC pseudogene regions. Gene is considered to have suboptimal coverage when >90% of the gene’s target nucleotides are not covered at >20x with mapping quality score (MQ>20) reads. The technology may have limited sensitivity to detect variants in genes marked with these symbols (please see the Panel content table above).

This test does not detect the following:

  • Complex inversions
  • Gene conversions
  • Balanced translocations
  • Some of the panels include the whole mitochondrial genome but not all (please see the Panel Content section)
  • Repeat expansion disorders unless specifically mentioned
  • Non-coding variants deeper than ±20 base pairs from exon-intron boundary unless otherwise indicated (please see above Panel Content / non-coding variants covered by the panel).

This test may not reliably detect the following:

  • Low level mosaicism in nuclear genes (variant with a minor allele fraction of 14.6% is detected with 90% probability)
  • Stretches of mononucleotide repeats
  • Low level heteroplasmy in mtDNA (>90% are detected at 5% level)
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments
  • Some disease causing variants present in mtDNA are not detectable from blood, thus post-mitotic tissue such as skeletal muscle may be required for establishing molecular diagnosis.

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.

The genes on the panel have been carefully selected based on scientific literature, mutation databases and our experience.

Our panels are sectioned from our high-quality, clinical grade NGS assay. Please see our sequencing and detection performance table for details regarding our ability to detect different types of alterations (Table).

Assays have been validated for various sample types including EDTA-blood, isolated DNA (excluding from formalin fixed paraffin embedded tissue), saliva and dry blood spots (filter cards). These sample types were selected in order to maximize the likelihood for high-quality DNA yield. The diagnostic yield varies depending on the assay used, referring healthcare professional, hospital and country. Plus analysis increases the likelihood of finding a genetic diagnosis for your patient, as large deletions and duplications cannot be detected using sequence analysis alone. Blueprint Genetics’ Plus Analysis is a combination of both sequencing and deletion/duplication (copy number variant (CNV)) analysis.

The performance metrics listed below are from an initial validation performed at our main laboratory in Finland. The performance metrics of our laboratory in Marlborough, MA, are equivalent.

Performance of Blueprint Genetics high-quality, clinical grade NGS sequencing assay for panels.

Sensitivity % (TP/(TP+FN)Specificity %
Single nucleotide variants99.89% (99,153/99,266)>99.9999%
Insertions, deletions and indels by sequence analysis
1-10 bps99.2% (7,745/7,806)>99.9999%
11-50 bps99.13% (2,524/2,546)>99.9999%
Copy number variants (exon level dels/dups)
1 exon level deletion (heterozygous)100% (20/20)NA
1 exon level deletion (homozygous)100% (5/5)NA
1 exon level deletion (het or homo)100% (25/25)NA
2-7 exon level deletion (het or homo)100% (44/44)NA
1-9 exon level duplication (het or homo)75% (6/8)NA
Simulated CNV detection
5 exons level deletion/duplication98.7%100.00%
Microdeletion/-duplication sdrs (large CNVs, n=37))
Size range (0.1-47 Mb)100% (25/25)
   
The performance presented above reached by Blueprint Genetics high-quality, clinical grade NGS sequencing assay with the following coverage metrics
   
Mean sequencing depth143X
Nucleotides with >20x sequencing coverage (%)99.86%

Performance of Blueprint Genetics Mitochondrial Sequencing Assay.

Sensitivity %Specificity %
ANALYTIC VALIDATION (NA samples; n=4)
Single nucleotide variants
Heteroplasmic (45-100%)100.0% (50/50)100.0%
Heteroplasmic (35-45%)100.0% (87/87)100.0%
Heteroplasmic (25-35%)100.0% (73/73)100.0%
Heteroplasmic (15-25%)100.0% (77/77)100.0%
Heteroplasmic (10-15%)100.0% (74/74)100.0%
Heteroplasmic (5-10%)100.0% (3/3)100.0%
Heteroplasmic (<5%)50.0% (2/4)100.0%
CLINICAL VALIDATION (n=76 samples)
All types
Single nucleotide variants n=2026 SNVs
Heteroplasmic (45-100%)100.0% (1940/1940)100.0%
Heteroplasmic (35-45%)100.0% (4/4)100.0%
Heteroplasmic (25-35%)100.0% (3/3)100.0%
Heteroplasmic (15-25%)100.0% (3/3)100.0%
Heteroplasmic (10-15%)100.0% (9/9)100.0%
Heteroplasmic (5-10%)92.3% (12/13)99.98%
Heteroplasmic (<5%)88.9% (48/54)99.93%
Insertions and deletions by sequence analysis n=40 indels
Heteroplasmic (45-100%) 1-10bp100.0% (32/32)100.0%
Heteroplasmic (5-45%) 1-10bp100.0% (3/3)100.0%
Heteroplasmic (<5%) 1-10bp100.0% (5/5)99,997%
SIMULATION DATA /(mitomap mutations)
Insertions, and deletions 1-24 bps by sequence analysis; n=17
Homoplasmic (100%) 1-24bp100.0% (17/17)99.98%
Heteroplasmic (50%)100.0% (17/17)99.99%
Heteroplasmic (25%)100.0% (17/17)100.0%
Heteroplasmic (20%)100.0% (17/17)100.0%
Heteroplasmic (15%)100.0% (17/17)100.0%
Heteroplasmic (10%)94.1% (16/17)100.0%
Heteroplasmic (5%)94.1% (16/17)100.0%
Copy number variants (separate artifical mutations; n=1500)
Homoplasmic (100%) 500 bp, 1kb, 5 kb100.0%100.0%
Heteroplasmic (50%) 500 bp, 1kb, 5 kb100.0%100.0%
Heteroplasmic (30%) 500 bp, 1kb, 5 kb100.0%100.0%
Heteroplasmic (20%) 500 bp, 1kb, 5 kb99.7%100.0%
Heteroplasmic (10%) 500 bp, 1kb, 5 kb99.0%100.0%
The performance presented above reached by following coverage metrics at assay level (n=66)
Mean of mediansMedian of medians
Mean sequencing depth MQ0 (clinical)18224X17366X
Nucleotides with >1000x MQ0 sequencing coverage (%) (clinical)100%
rho zero cell line (=no mtDNA), mean sequencing depth12X

The target region for each gene includes coding exons and ±20 base pairs from the exon-intron boundary. In addition, the panel includes non-coding and regulatory variants if listed above (Non-coding variants covered by the panel). Some regions of the gene(s) may be removed from the panel if specifically mentioned in the ‘Test limitations” section above. If the test includes the mitochondrial genome the target region gene list contains the mitochondrial genes. 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. Our pipeline is streamlined to maximize sensitivity without sacrificing specificity. We have incorporated a number of reference population databases and mutation databases including, but not limited, to 1000 Genomes Project, gnomAD, ClinVar and HGMD into our clinical interpretation software to make the process effective and efficient. For missense variants, in silico variant prediction tools such as  SIFT, PolyPhen,MutationTaster are used to assist with variant classification. Through our online ordering and statement reporting system, Nucleus, ordering providers have access to the details of the analysis, including patient specific sequencing metrics, a gene level coverage plot and a list of regions with suboptimal coverage (<20X for nuclear genes and <1000X for mtDNA) if applicable. This reflects our mission to build fully transparent diagnostics where ordering providers can easily visualize the crucial details of the analysis process.

We provide customers with comprehensive clinical report available on the market. Clinical interpretation requires a fundamental understanding of clinical genetics and genetic principles. At Blueprint Genetics, our Ph.D. molecular geneticists, medical professionals, and other highly experienced experts prepare clinical reports by evaluating the identified variants in the context of the phenotypic information provided in the requisition form.

Our goal is to provide clinically meaningful reports that are understandable for all medical professionals regardless of whether they have formal training in genetics. Variant classification is the cornerstone of clinical interpretation and resulting patient management decisions. Our classifications follow the ACMG guideline 2015. Sequence and copy number variants classified as pathogenic, likely pathogenic, and variants of uncertain significance (VUS) are confirmed using bidirectional Sanger sequencing or by orthogonal methods such as qPCR/ddPCR when they do not meet our stringent NGS quality metrics for a true positive call.

Our clinical report includes tables for sequence and copy number variants that include basic variant information (genomic coordinates, HGVS nomenclature, zygosity, allele frequencies, in silico predictions, phenotypes, and classification of the variant). In addition, the statement includes detailed descriptions of the variant, gene, and phenotype(s), including the role of the specific gene in human disease, the mutation profile, information about the gene’s variation in population cohorts, and detailed information about related phenotypes. We also provide links to the references, abstracts, and variant databases used to help ordering providers further evaluate the reported findings if desired.

The panel report is divided into primary findings and additional findings sections. Variants reported as primary findings are known disease-causing variants or rare variants that could potentially explain the patient’s phenotype as described to the laboratory at the time of interpretation. The conclusion summarizes all the existing information and provides our rationale for the classification of the variant.

Variants reported as additional findings are variants that are not likely or sufficient to cause the tested patient’s phenotype, based on the current knowledge. Additional findings in panel reports include variants that are, for example, carrierships of single heterozygous variants in genes associated with autosomal recessive disorders, variants of uncertain significance in genes associated with autosomal dominant disorders (if pathogenic or likely pathogenic variants considered sufficient to explain the patient’s phenotype are reported as primary findings), or risk alleles identified in genes included in the panel.

Identification of pathogenic or likely pathogenic variants in dominant disorders or their combinations in different alleles in recessive disorders are considered molecular confirmation of the clinical diagnosis. In these cases, family member testing can be used for risk stratification. We do not recommend using variants of uncertain significance (VUS) for family member risk stratification or patient management. Genetic counseling is recommended.

Our interpretation team analyzes millions of variants from thousands of individuals with rare diseases. Our internal database and our understanding of variants and related phenotypes increases with every case analyzed. Our laboratory is therefore well positioned to reclassify previously reported variants as new information becomes available. If a variant previously reported as a primary or secondary finding by Blueprint Genetics is reclassified so that it becomes diagnostic (VUS to P/LP) or earlier molecular diagnosis is removed (P/LP to VUS, LB, B), our laboratory will issue a follow-up statement to the original ordering healthcare provider at no additional cost.