Comprehensive Hematology Panel
Updated

Last modified: Mar 21, 2018

Summary

  • Is a 238 gene panel that includes assessment of non-coding variants
  • Offers comprehensive genetic diagnostics for a broad range of hematological disorders varying from bone marrow failure to specific disorders affecting different cell populations or factors involved in hemostasis.

Analysis methods

  • PLUS
  • SEQ
  • DEL/DUP

Availability

3-4 weeks

Number of genes

238

Test code

HE0101

CPT codes

SEQ 81216
SEQ 81406
SEQ 81408
DEL/DUP 81479

Summary

The Blueprint Genetics Comprehensive Hematology Panel (test code HE0101):

  • Is a 238 gene panel that includes assessment of selected non-coding disease-causing variants
  • Is available as PLUS analysis (sequencing analysis and deletion/duplication analysis), sequencing analysis only or deletion/duplication analysis only

Sample Requirements

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 3μg
  • 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.

Genes in the Comprehensive Hematology Panel and their clinical significance

Gene Associated phenotypes Inheritance ClinVar HGMD
ABCA3 Interstitial lung disease, Surfactant metabolism dysfunction, pulmonary AD/AR 11 181
ABCB7 Anemia, sideroblastic, and spinocerebellar ataxia XL 8 9
ABCG5 Sitosterolemia AR 10 36
ABCG8 Sitosterolemia AR 11 33
ACD Dyskeratosis congenita, autosomal dominant 6, Dyskeratosis congenita, autosomal recessive 7 AD/AR 2 8
ACTB* Baraitser-Winter syndrome AD 38 27
ACTN1 Bleeding disorder, platelet- AD 6 24
ADAMTS13 Schulman-Upshaw syndrome, Thrombotic thrombocytopenic purpura, familial AR 26 162
AK2 Reticular dysgenesis AR 14 17
ALAS2 Anemia, sideroblastic, Protoporphyria, erythropoietic XL 26 94
AMN Megaloblastic anemia-1, Norwegian AR 25 32
ANK1 Spherocytosis AD/AR 14 83
ANKRD26 Thrombocytopenia AD 6 21
AP3B1 Hermansky-Pudlak syndrome AR 14 25
AP3D1 Hermansky-Pudlak syndrome 10 1 2
ARPC1B Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease AR 2 3
ATM Breast cancer, Ataxia-Telangiectasia AD/AR 646 923
ATR Cutaneous telangiectasia and cancer syndrome, Seckel syndrome AD/AR 8 18
ATRX Carpenter-Waziri syndrome, Alpha-thalassemia/mental retardation syndrome, Holmes-Gang syndrome, Juberg-Marsidi syndrome, Smith-Fineman-Myers syndrome, Mental retardation-hypotonic facies syndrome XL 54 155
BLM Bloom syndrome AR 83 91
BLOC1S3 Hermansky-Pudlak syndrome AR 2 2
BLOC1S6 Hermansky-Pudlak syndrome AR 1 1
BRAF* LEOPARD syndrome, Noonan syndrome, Cardiofaciocutaneous syndrome AD 131 62
BRCA1* Pancreatic cancer, Breast-ovarian cancer, familial AD 2448 2175
BRCA2 Fanconi anemia, Medulloblastoma, Glioma susceptibility, Pancreatic cancer, Wilms tumor, Breast-ovarian cancer, familial AD/AR 2771 2045
BRIP1 Fanconi anemia, Breast cancer AD/AR 122 130
C15ORF41 Congenital dyserythropoietic anemia AR 3 2
CBL Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia AD 23 36
CDAN1 Anemia, dyserythropoietic congenital AR 10 42
CDKN2A Melanoma, familial, Melanoma-pancreatic cancer syndrome AD 69 218
CEBPA Acute myeloid leukemia, familial AD 15 10
CLCN7 Osteopetrosis AD/AR 11 90
CLPB 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia (MEGCANN) AR 21 21
CSF2RA* Surfactant metabolism dysfunction, pulmonary XL 2 17
CSF3R Neutrophilia, hereditary AD 10 10
CTC1 Cerebroretinal microangiopathy with calcifications and cysts AR 15 29
CTSC Periodontitis, juvenile, Haim-Munk syndrome, Papillon-Lefevre syndrome AR 16 91
CUBN* Megaloblastic anemia-1, Finnish AR 34 52
CXCR4 Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome AD 5 15
CYB5R3 Methemoglobinemia due to methemoglobin reductase deficiency AR 20 66
CYCS* Thrombocytopenia AD 2 3
DDX41 Familial myeloproliferative/lymphoproliferative neoplasms, multiple types, susceptibility to 7 13
DHFR* Megaloblastic anemia due to dihydrofolate reductase deficiency AR 2 5
DKC1 Hoyeraal-Hreidarsson syndrome, Dyskeratosis congenita XL 47 71
DNAJC21 Bone marrow failure syndrome 3 5 8
DTNBP1 Hermansky-Pudlak syndrome AR 2 2
EGLN1* Hemoglobin, high altitude adapation AD 3 30
ELANE Neutropenia AD 37 213
EPAS1 Erthyrocytosis, familial 4 AD 3 17
EPB41 Ellipsocytosis 1 AR 6 12
EPB42 Spherocytosis AR 8 14
EPCAM Diarrhea 5, with tufting enteropathy, congenital, Colorectal cancer, hereditary nonpolyposis AD/AR 20 69
EPOR Erythrocytosis, familial, 1 AD 4 23
ERCC4 Fanconi anemia, Xeroderma pigmentosum AR 11 43
ERCC6L2 Bone marrow failure syndrome 2 AR 4 2
ETV6 Thrombocytopenia 5 AD 10 32
F2 Thrombophilia due to thrombin defect, Prothrombin deficiency, congenital AD/AR 14 62
F5 Factor V deficiency, Thrombophilia due to activated protein C resistance AD/AR 19 151
F7 Factor VII deficiency AR 27 295
F8* Hemophilia A XL 290 3121
F9 Hemophilia B, Warfarin sensitivity, Thrombophilia, due to factor IX defect XL 112 1277
F10 Factor X deficiency AR 16 149
F11 Factor XI deficiency AD/AR 55 254
F12 Angioedema AD/AR 7 52
F13A1 Factor XIIIA deficiency AR 20 180
F13B Factor XIIIB deficiency AR 4 18
FADD Infections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovascular malformations AR 2 1
FANCA Fanconi anemia AR 59 520
FANCB Fanconi anemia XL 10 18
FANCC Fanconi anemia AR 63 45
FANCD2* Fanconi anemia AR 13 56
FANCE Fanconi anemia AR 5 16
FANCF Fanconia anemia AR 7 15
FANCG Fanconi anemia AR 13 84
FANCI Fanconi anemia AR 13 40
FANCL Fanconi anemia AR 7 20
FANCM Fanconi anemia AR 1 43
FAS Autoimmune lymphoproliferative syndrome AD/AR 24 129
FASLG Autoimmune lymphoproliferative syndrome, type IB AD 3 9
FGA Afibrinogenemia, congenital, Dysfibrinogenemia, congenital, Hypodysfibrinogenemia, congenital, Familial visceral amyloidosis AD/AR 10 134
FGB Afibrinogenemia, congenital, Dysfibrinogenemia, congenital, Hypodysfibrinogenemia, congenital AD/AR 6 87
FGG Afibrinogenemia, congenital, Hypodysfibrinogenemia, Dysfibrinogenemia, congenital, Hypodysfibrinogenemia, congenital AD/AR 5 123
FLI1 Thrombocytopenia, Paris-Trousseau type, Bleeding disorder, platelet type 21 AD 7 6
FLNA Frontometaphyseal dysplasia, Osteodysplasty Melnick-Needles, Otopalatodigital syndrome type 1, Otopalatodigital syndrome type 2, Terminal osseous dysplasia with pigmentary defects XL 102 220
FYB Thrombocytopenia 3 AR 2
G6PC3 Neutropenia, severe congenital, Dursun syndrome AR 12 37
G6PD Glucose-6-phosphate dehydrogenase deficiency XL 39 221
GATA1 Anemia, without thrombocytopenia, Thrombocytopenia with beta-thalessemia,, Dyserythropoietic anemia with thrombocytopenia XL 17 15
GATA2 Myelodysplastic syndrome, Chronic neutropenia associated with monocytopenia, evolving to myelodysplasia and acute myeloid leukemia, Acute myeloid leukemia, Emberger syndrome, Immunodeficiency AD 22 105
GFI1 Neutropenia, severe congenital, 2 autosomal dominant, Neutropenia, nonimmune chronic idiopathic, of adults AD 2 5
GFI1B Bleeding disorder, platelet-type, 17 AD 5 8
GGCX Pseudoxanthoma elasticum-like disorder with multiple coagulation factor deficiency, Vitamin K-dependent clotting factors, combined deficiency AD/AR/Digenic 13 38
GINS1 Immunodeficiency AR 4
GP1BA Pseudo-von Willebrand disease, Bernard-Soulier syndrome AD/AR 7 69
GP1BB Giant platelet disorder, isolated, Bernard-Soulier syndrome AD/AR 5 53
GP9 Bernard-Soulier syndrome AR 6 40
GPI Hemolytic anemia, nonspherocytic due to glucose phosphate isomerase deficiency AD 10 37
GPR143 Nystagmus, congenital, Ocular albinism XL 19 148
GSS Glutathione synthetase deficiency AR 7 34
HAX1 Neutropenia, severe congenital AR 9 19
HBA1* Alpha-thalassemia (Hemoglobin Bart syndrome), Alpha-thalassemia (Hemoglobin H disease) AR/Digenic 15 202
HBA2*,# Alpha-thalassemia (Hemoglobin Bart syndrome), Alpha-thalassemia (Hemoglobin H disease) AR/Digenic 41 277
HBB Sickle cell disease, Thalassemia-beta, dominant inclusion body, Other Thalassemias/Hemoglobinopathies, Beta-thalassemia AD/AR/Digenic 199 850
HFE Hemochromatosis AR/Digenic 9 53
HOXA11 Radioulnar synostosis with amegakaryocytic thrombocytopenia AD 1 1
HPS1* Hermansky-Pudlak syndrome AR 27 45
HPS3* Hermansky-Pudlak syndrome AR 8 13
HPS4 Hermansky-Pudlak syndrome AR 15 18
HPS5 Hermansky-Pudlak syndrome AR 20 27
HPS6 Hermansky-Pudlak syndrome AR 13 26
HRAS Costello syndrome, Congenital myopathy with excess of muscle spindles AD 39 27
IFNGR2 Immunodeficiency AR 4 17
IKZF1# Immunodeficiency, common variable, 13 7 11
ITGA2 Fetal and neonatal alloimmune thrombocytopenia AD/AR 3
ITGA2B Glanzmann thrombasthenia AD/AR 20 208
ITGB3 Bleeding disorder, platelet-, Thrombocytopenia, neonatal alloimmune, Glanzmann thrombasthenia AD/AR 18 148
ITK Lymphoproliferative syndrome AR 3 10
JAGN1 Neutropenia, severe congenital AR 8 8
JAK2 Thrombocythemia 3 AD 12 15
KLF1 Anemia, dyserythropoietic congenital, Blood group, Lutheran inhibitor AD/BG 16 46
KRAS* Noonan syndrome, Cardiofaciocutaneous syndrome AD 59 31
LAMTOR2 Immunodeficiency due to defect in MAPBP-interacting protein AR 1 1
LMAN1 Combined factor V and VIII deficiency AR 5 37
LPIN2 Majeed syndrome AR 7 10
LYST* Chediak-Higashi syndrome AR 46 87
MAGT1 Immunodeficiency, with magnesium defect, Epstein-Barr virus infection and neoplasia XL 5 14
MAP2K1 Cardiofaciocutaneous syndrome AD 43 21
MAP2K2 Cardiofaciocutaneous syndrome AD 21 34
MASTL Thrombocytopenia AD 3
MCFD2 Factor V & Factor VIII, combined deficiency of AR 8 20
MECOM Radioulnar synostosis with amegakaryocytic thrombocytopenia 2 AD 3 4
MKL1 Primary immunodeficiency AR 3
MLH1 Muir-Torre syndrome, Endometrial cancer, Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposis AD/AR 748 1119
MPL Thrombocythemia, Amegakaryocytic thrombocytopenia AD/AR 21 49
MSH2 Muir-Torre syndrome, Endometrial cancer, Colorectal cancer, hereditary nonpolyposis,, Mismatch repair cancer syndrome AD/AR 803 1147
MSH6 Endometrial cancer, Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposis AD/AR 480 472
MTHFD1 Severe combined immunodeficiency AR 9
MTR Methylmalonic acidemia AR 12 40
MYH9 Sebastian syndrome, May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, Macrothrombocytopenia and progressive sensorineural deafness AD 21 113
MYO5A Griscelli syndrome AR 5 6
NBEAL2 Gray platelet syndrome AR 10 43
NBN Breast cancer, Nijmegen breakage syndrome AD/AR 95 65
NF1* Watson syndrome, Neurofibromatosis, Neurofibromatosis-Noonan syndrome AD 592 2681
NHP2 Dyskeratosis congenita AR 3 3
NOP10 Dyskeratosis congenita AR 1 1
NRAS Noonan syndrome AD 31 14
NT5C3A Uridine 5-prime monophosphate hydrolase deficiency, hemolytic anemia due to AR 10 27
OCA2 Albinism, brown oculocutaneous, Albinism, oculocutaneous, Skin/hair/eye pigmentation AD/AR 39 231
P2RY12 Bleeding disorder, platelet- AD/AR 3 12
PALB2 Fanconi anemia, Pancreatic cancer, Breast cancer AD/AR 317 274
PARN* Pulmonary fibrosis and/or bone marrow failure, Dyskeratosis congenita AD/AR 15 24
PAX5 Pre-B cell acute lymphoblastic leukemia AD 5
PC Pyruvate carboxylase deficiency AR 29 39
PDHA1 Leigh syndrome, Pyruvate dehydrogenase E1-alpha deficiency XL 51 170
PDHX Pyruvate dehydrogenase E3-binding protein deficiency AR 14 22
PGM3 Immunodeficiency 23 AR 12 12
PIEZO1 Dehydrated hereditary stomatocytosis, Lympehedema, hereditary III AD 21 35
PKLR Pyruvate kinase deficiency AR 16 263
PMS2* Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposis AD/AR 196 284
PRF1 Lymphoma, non-Hodgkin, Aplastic anemia, adult-onset, Hemophagocytic lymphohistiocytosis AR 17 169
PRKACG Bleeding disorder, platelet-type, 19 AR 1
PROC Thrombophilia, hereditary AD/AR 29 384
PROS1* Thrombophilia, hereditary AD/AR 17 412
PTPN11 LEOPARD syndrome, Noonan syndrome, Metachondromatosis AD 124 135
PUS1 Mitochondrial myopathy and sideroblastic anemia AR 7 7
RAB27A Griscelli syndrome, Elejalde syndrome AR 14 49
RAC2 Neutrophil immunodeficiency syndrome AD 1 3
RAD51C Fanconi anemia, Breast-ovarian cancer, familial AD/AR 60 95
RBM8A*,# Thrombocytopenia - absent radius AD/AR 4 9
RECQL4 Baller-Gerold syndrome, RAPADILINO syndrome, Rothmund-Thomson syndrome AR 43 96
REN Hyperuricemic nephropathy AD 8 18
RHAG Overhydrated hereditary stomatocytosis, Anemia, hemolytic, Rh-null, regulator type, Anemia, hemolytic,Rh-Mod type, RHAG blood group AD/AR/BG 13 21
RIT1 Noonan syndrome AD 21 24
RNF168 RIDDLE syndrome AR 3 4
RPL5 Diamond-Blackfan anemia AD 10 68
RPL11 Diamond-Blackfan anemia AD 7 41
RPL15* Diamond-Blackfan anemia AD 2 2
RPL35A Diamond-Blackfan anemia AD 4 14
RPS7 Diamond-Blackfan anemia AD 2 9
RPS10 Diamond-Blackfan anemia AD 3 5
RPS19 Diamond-Blackfan anemia AD 18 168
RPS24 Diamond-Blackfan anemia AD 5 9
RPS26 Diamond-Blackfan anemia AD 8 29
RPS29 Diamond-Blackfan anemia AD 3 3
RTEL1 Pulmonary fibrosis and/or bone marrow failure, Dyskeratosis congenita AD/AR 32 44
RUNX1 Platelet disorder, familial, with associated myeloid malignancy AD 24 82
SAMD9 Mirage syndrome, Tumoral calcinosis, normophosphatemic AR 5 17
SAMD9L Ataxia-pancytopenia syndrome 2 4
SBDS* Aplastic anemia, Shwachman-Diamond syndrome, Severe spondylometaphyseal dysplasia AD/AR 18 88
SEC23B Anemia, dyserythropoietic congenital AR 14 111
SERPINC1 Antithrombin III deficiency AD/AR 43 378
SFTPB Surfactant metabolism dysfunction, pulmonary AR 5 27
SFTPC Surfactant metabolism dysfunction, pulmonary AD 7 77
SH2D1A Lymphoproliferative syndrome XL 14 125
SLC4A1 Spherocytosis, Ovalcytosis, Renal tubular acidosis, distal, with hemolytic anemia, Cryohydrocytosis AD/AR/BG 31 114
SLC19A2 Thiamine-responsive megaloblastic anemia syndrome AR 11 49
SLC25A38 Anemia, sideroblastic 2, pyridoxine-refractory AR 6 24
SLC37A4 Glycogen storage disease AR 27 108
SLC45A2 Skin/hair/eye pigmentation, Oculocutaneous albinism AD/AR 15 111
SLC46A1 Folate malabsorption AR 17 20
SLFN14 Thrombocytopenia AD/AR 4 4
SLX4 Fanconi anemia AR 11 49
SMARCD2 Specific granule defiency 2 3
SOS1 Noonan syndrome AD 45 66
SPTA1 Spherocytosis, Ellipsocytosis, Pyropoikilocytosis AD/AR 23 40
SPTB Spherocytosis, Anemia, neonatal hemolytic, Ellipsocytosis AD/AR 15 67
SRC Thrombocytopenia, autosomal dominant, 6 2
SRP72* Bone marrow failure syndrome 1 AD 2 2
STX11 Hemophagocytic lymphohistiocytosis, familial AR 5 15
STXBP2 Hemophagocytic lymphohistiocytosis, familial AR 8 62
TBXA2R Bleeding disorder, platelet- AD 6
TCN2 Transcobalamin II deficiency AR 8 33
TERC Aplastic anemia, Pulmonary fibrosis and/or bone marrow failure, telomere-related, Dyskeratosis congenita AD 37 67
TERT Aplastic anemia, Pulmonary fibrosis and/or bone marrow failure, telomere-related, Dyskeratosis congenita AD/AR 44 149
TF Atransferrinemia AR 8 16
THBD Thrombophilia due to thrombomodulin defect, Hemolytic uremic syndrome, atypical AD 5 21
THPO Thrombocythemia 1 AD 4 6
TINF2 Revesz syndrome, Dyskeratosis congenita AD 23 34
TMPRSS6 Iron-refractory iron deficiency anemia AR 13 75
TP53 Colorectal cancer, Li-Fraumeni syndrome, Ependymoma, intracranial, Choroid plexus papilloma, Breast cancer, familial, Adrenocortical carcinoma, Osteogenic sarcoma, Hepatoblastoma, Non-Hodgkin lymphoma AD 340 405
TPI1 Triosephosphate isomerase deficiency AR 8 19
TRNT1 Retinitis pigmentosa and erythrocytic microcytosis AR 12 21
TUBB1 Macrothrombocytopenia AD 2 7
TYR* Albinism, oculocutaneous AR 69 391
TYRP1 Albinism, oculocutaneous AR 10 36
UNC13D Hemophagocytic lymphohistiocytosis, familial AR 14 141
USB1 Poikiloderma with neutropenia AR 4 22
VKORC1 Drug metabolism, VKORC1-related, Vitamin K-dependent clotting factors, combined deficiency AD/AR 4 27
VPS13B Cohen syndrome AR 231 197
VPS45 Neutropenia, severe congenital, 5, autosomal recessive AR 3 4
VWF* Von Willebrand disease AD/AR 50 847
WAS Neutropenia, severe congenital, Thrombocytopenia, Wiskott-Aldrich syndrome XL 44 431
WDR1 6
WIPF1 Wiskott-Aldrich syndrome 2 AR 2 2
WRAP53 Dyskeratosis congenita AR 7 5
XIAP* Lymphoproliferative syndrome XL 4 83
XRCC2 Hereditary breast cancer AD/AR 8 15
YARS2 Myopathy, lactic acidosis, and sideroblastic anemia AR 25 11

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

# The gene has suboptimal coverage (means <90% of the gene’s target nucleotides are covered at >20x with mapping quality score (MQ>20) reads).

The sensitivity to detect variants may be limited in genes marked with an asterisk (*) or number sign (#)

Gene refers to the HGNC approved gene symbol; Inheritance refers to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR), 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 Orphanet databases.

Non-coding variants covered by the panel

Gene Genomic location HG19 HGVS RefSeq RS-number
ABCA3 Chr16:2376495 c.-26-2A>G NM_001089.2
ABCA3 Chr16:2358644 c.1112-20G>A NM_001089.2 rs746701685
ABCA3 Chr16:2333457 c.3863-98C>T NM_001089.2 rs189077405
ALAS2 ChrX:55054634 c.-15-2186C>G NM_000032.4
ALAS2 ChrX:55054635 c.-15-2187T>C NM_000032.4
ALAS2 ChrX:55054636 c.-15-2188A>G NM_000032.4
ALAS2 ChrX:55057617 c.-258C>G NM_000032.4 rs140772352
AMN Chr14:103396458 c.1007-29_1006+36delTCGCCCCGCCGCGGG NM_030943.3 rs386834162
AMN Chr14:103396444 c.1007-31_1006+34delCCTCGCCCCGCCGCG NM_030943.3 rs386834161
AMN Chr14:103395424 c.514-34G>A NM_030943.3 rs144077391
ANK1 Chr8:41655127 c.-73_-72delTG NM_020476.2 rs786205242
ANK1 Chr8:41655209 c.127-39554G>A NM_001142446.1 rs183894680
ANK1 Chr8:41566510 c.1900-17G>A NM_001142446.1 rs786205243
ANK1 Chr8:41566511 c.1900-18C>A NM_001142446.1
ANKRD26 Chr10:27389389 c.-134G>A NM_014915.2 rs863223318
ATM Chr11:108093770 c.-174A>G NM_000051.3
ATM Chr11:108098321 c.-30-1G>T NM_000051.3 rs869312754
ATM Chr11:108094508 c.-31+595G>A NM_000051.3
ATM Chr11:108121024 c.1236-404C>T NM_000051.3
ATM Chr11:108138753 c.2639-384A>G NM_000051.3
ATM Chr11:108141209 c.2839-579_2839-576delAAGT NM_000051.3
ATM Chr11:108151710 c.3403-12T>A NM_000051.3 rs201370733
ATM Chr11:108158168 c.3994-159A>G NM_000051.3 rs864622543
ATM Chr11:108179837 c.5763-1050A>G NM_000051.3 rs774925473
BRCA1 Chr17:41196424 c.*1271T>C NM_007294.3
BRCA1 Chr17:41197637 c.*58C>T NM_007294.3 rs137892861
BRCA1 Chr17:41196977 c.*718A>G NM_007294.3
BRCA1 Chr17:41196895 c.*800T>C NM_007294.3
BRCA1 Chr17:41256984 c.213-11T>G NM_007294.3 rs80358061
BRCA1 Chr17:41256985 c.213-12A>G NM_007294.3 rs80358163
BRCA1 Chr17:41256988 c.213-15A>G NM_007294.3
BRCA1 Chr17:41209164 c.5194-12G>A NM_007294.3 rs80358079
BRCA1 Chr17:41199745 c.5407-25T>A NM_007294.3 rs758780152
BRCA2 Chr13:32889805 c.-40+1G>A NM_000059.3
BRCA2 Chr13:32953872 c.8954-15T>G NM_000059.3
BRCA2 Chr13:32971007 c.9502-28A>G NM_000059.3 rs397508059
BRIP1 Chr17:59858864 c.1629-498A>T NM_032043.2
CDKN2A Chr9:21974860 c.-34G>T NM_000077.4 rs1800586
CDKN2A Chr9:21973573 c.150+1104C>A NM_000077.4 rs756102261
CDKN2A Chr9:21972311 c.151-1104C>G NM_000077.4
CDKN2A Chr9:21968346 c.458-105A>G NM_000077.4
CLCN7 Chr16:1506057 c.916+57A>T NM_001287.5
CTSC Chr11:88070895 c.-55C>A NM_001814.4 rs766114323
CUBN Chr10:17088532 c.3330-439C>G NM_001081.3 rs386833782
DKC1 ChrX:153991100 c.-141C>G NM_001363.3
DKC1 ChrX:153991099 c.-142C>G NM_001363.3 rs199422241
DKC1 ChrX:153993704 c.85-15T>C NM_001363.3
EPCAM Chr2:47606078 c.556-14A>G NM_002354.2 rs376155665
F11 Chr4:187186995 c.-456G>A NM_000128.3
F13A1 Chr6:6320808 c.-19+12A>T NM_000129.3 rs2815822
F2 Chr11:46761064 c.*106T>A NM_000506.3
F2 Chr11:46761066 c.*108C>T NM_000506.3 rs562369397
F2 Chr11:46761055 c.*97G>A NM_000506.4 rs1799963
F2 Chr11:46742048 c.241-25C>G NM_000506.3
F5 Chr1:169521984 c.1119-12C>G NM_000130.4
F5 Chr1:169521527 c.1296+268A>G NM_000130.4
F5 Chr1:169494158 c.5717-12T>A NM_000130.4
F7 Chr13:113764993 c.131-11G>A NM_000131.4
F7 Chr13:113770192 c.571+78G>A NM_000131.4 rs764741909
F7 Chr13:113771068 c.572-12T>A NM_000131.4
F8 ChrX:154251045 c.-218T>C NM_000132.3
F8 ChrX:154251046 c.-219C>T NM_000132.3
F8 ChrX:154251048 c.-221T>A NM_000132.3
F8 ChrX:154251082 c.-255A>G NM_000132.3
F8 ChrX:154251084 c.-257T>C/G NM_000132.3
F8 ChrX:154251687 c.-860A>G NM_000132.3
F8 ChrX:154251793 c.-966G>T NM_000132.3
F8 ChrX:154249118 c.143+1567A>G NM_000132.3
F8 ChrX:154227886 c.144-11T>G NM_000132.3
F8 ChrX:154227901 c.144-26A>T NM_000132.3
F8 ChrX:154189458 c.1444-15C>A NM_000132.3
F8 ChrX:154189025 c.1537+325A>G NM_000132.3
F8 ChrX:154185464 c.1538-18G>A NM_000132.3
F8 ChrX:154176219 c.1904-37G>A NM_000132.3 rs367615232
F8 ChrX:154175961 c.2113+12T>A NM_000132.3
F8 ChrX:154221439 c.389-16T>G NM_000132.3
F8 ChrX:154132892 c.5587-93C>T NM_000132.3
F8 ChrX:154131652 c.5998+529C>T NM_000132.3
F8 ChrX:154130719 c.5999-277G>A NM_000132.3
F8 ChrX:154131240 c.5999-798G>A NM_000132.3
F8 ChrX:154219579 c.601+1632G>A NM_000132.3 rs387906429
F8 ChrX:154215591 c.602-11T>G NM_000132.3
F8 ChrX:154215612 c.602-32A>G NM_000132.3
F8 ChrX:154091516 c.6430-14A>G NM_000132.3
F8 ChrX:154213089 c.671-11T>C NM_000132.3
F8 ChrX:154084603 c.6900+4104A>T NM_000132.3
F8 ChrX:154197841 c.788-14T>G NM_000132.3
F9 ChrX:138645387 c.*1157A>G NM_000133.3
F9 ChrX:138645598 c.*1368A>G NM_000133.3
F9 ChrX:138612907 c.-17A>C/G NM_000133.3
F9 ChrX:138612906 c.-18A>G/T NM_000133.3
F9 ChrX:138612905 c.-19C>G NM_000133.3
F9 ChrX:138612903 c.-21C>G NM_000133.3
F9 ChrX:138612902 c.-22T>C NM_000133.3
F9 ChrX:138612901 c.-23T>C NM_000133.3
F9 ChrX:138612900 c.-24T>A NM_000133.3
F9 ChrX:138612890 c.-34A>G/T NM_000133.3
F9 ChrX:138612889 c.-35G>A/C NM_000133.3
F9 ChrX:138612886 c.-38A>G NM_000133.3
F9 ChrX:138612876 c.-48G>C NM_000133.3
F9 ChrX:138612875 c.-49T>A/C NM_000133.3
F9 ChrX:138612874 c.-50T>C/G NM_000133.3
F9 ChrX:138612872 c.-52C>G/T NM_000133.3
F9 ChrX:138612871 c.-53A>G NM_000133.3
F9 ChrX:138612869 c.-55G>A/C/T NM_000133.3
F9 ChrX:138619496 c.253-25A>G/T NM_000133.3
F9 ChrX:138623223 c.278-12C>G/T NM_000133.3
F9 ChrX:138623222 c.278-13A>G NM_000133.3
F9 ChrX:138630663 c.520+13A>G NM_000133.3
F9 ChrX:138633441 c.723+18T>A NM_000133.3
FANCA Chr16:89849346 c.1567-20A>G NM_000135.2 rs775154397
FANCA Chr16:89836805 c.2223-138A>G NM_000135.2
FANCA Chr16:89836111 c.2504+134A>G NM_000135.2
FANCA Chr16:89831215 c.2778+83C>G NM_000135.2 rs750997715
FANCA Chr16:89818822 c.2982-192A>G NM_000135.2
FANCA Chr16:89816056 c.3239+82T>G NM_000135.2
FANCA Chr16:89864654 c.893+920C>A NM_000135.2
FANCC Chr9:98011653 c.-78-2A>G NM_000136.2 rs587779898
FANCD2 Chr3:10083186 c.696-121C>G NM_033084.3
FANCI Chr15:89825208 c.1583+142C>T NM_001113378.1
FAS Chr10:90770494 c.506-16A>G NM_000043.4
FASLG Chr1:172628081 c.-261T>C NM_000639.1
FGA Chr4:155513028 c.-1189C>T NM_021871.2
FGB Chr4:155486360 c.115-600A>G NM_005141.4
FGB Chr4:155490472 c.958+13C>T NM_005141.4 rs606231223
FGG Chr4:155527225 c.1129+632A>G NM_021870.2 rs2066862
FGG Chr4:155530122 c.667-320A>T NM_021870.2
GATA1 ChrX:48649496 c.-19-2A>G NM_002049.3
GATA2 Chr3:128202171 c.1017+532T>A NM_032638.4
GATA2 Chr3:128202131 c.1017+572C>T NM_032638.4
GINS1 Chr20:25388409 c.-48C>G NM_021067.3
GINS1 Chr20:25388397 c.-60A>G NM_021067.3
GP1BB Chr22:19710933 c.-160C>G NM_000407.4 rs730882059
GPR143 ChrX:9711844 c.659-131T>G NM_000273.2
GPR143 ChrX:9708630 c.885+748G>A NM_000273.2
GSS Chr20:33543525 c.-9+5G>A NM_000178.2
HBA2 Chr16:223691 c.*92A>G NM_000517.4 rs63750067
HBB Chr11:5246720 c.*108A>C/G NM_000518.4
HBB Chr11:5246718 c.*110T>A/C NM_000518.4 rs33978907
HBB Chr11:5246718 c.*110T>G NM_000518.4
HBB Chr11:5246713 c.*110_*114delTAAAA NM_000518.4 rs35949130
HBB Chr11:5246713 c.*110_*114delTAAAA NM_000518.4 rs606231219
HBB Chr11:5246713 c.*110_*114delTAAAA NM_000518.4 rs606231219,rs35949130
HBB Chr11:5246717 c.*111A>G NM_000518.4 rs63751128
HBB Chr11:5246716 c.*112A>G/T NM_000518.4 rs63750954
HBB Chr11:5246715 c.*113A>G NM_000518.4 rs33985472
HBB Chr11:5246699 c.*129T>C NM_000518.4
HBB Chr11:5246696 c.*132C>A/T NM_000518.4
HBB Chr11:5246796 c.*32A>C NM_000518.4
HBB Chr11:5246781 c.*47C>G NM_000518.4
HBB Chr11:5246754 c.*74A>G NM_000518.4 rs369101035
HBB Chr11:5248351 c.-100G>A NM_000518.4 rs281864524
HBB Chr11:5248357 c.-106G>C NM_000518.4 rs63750681
HBB Chr11:5248372 c.-121C>T NM_000518.4 rs281864518
HBB Chr11:5248374 c.-123A>T NM_000518.4
HBB Chr11:5248377 c.-126C>A NM_000518.4
HBB Chr11:5248378 c.-127G>C NM_000518.4
HBB Chr11:5248263 c.-12C>T NM_000518.4 rs113115948
HBB Chr11:5248387 c.-136C>A/G/T NM_000518.4 rs33994806
HBB Chr11:5248388 c.-137C>A/G/T NM_000518.4 rs33941377
HBB Chr11:5248389 c.-138C>A/T NM_000518.4 rs33944208
HBB Chr11:5248391 c.-140C>T NM_000518.4 rs34999973
HBB Chr11:5248393 c.-142C>T NM_000518.4 rs34883338
HBB Chr11:5248394 c.-143C>G NM_000518.4 rs63751043
HBB Chr11:5248402 c.-151C>T NM_000518.4 rs63751208
HBB Chr11:5248403 c.-152C>A NM_000518.4
HBB Chr11:5248269 c.-18C>G NM_000518.4 rs34135787
HBB Chr11:5248272 c.-21T>A NM_000518.4
HBB Chr11:5248491 c.-240G>A NM_000518.4 rs753344875
HBB Chr11:5248524 c.-273T>C NM_000518.4 rs139703273
HBB Chr11:5248280 c.-29G>A NM_000518.4 rs34704828
HBB Chr11:5248282 c.-31C>T NM_000518.4 rs63750628
HBB Chr11:5248294 c.-43C>T NM_000518.4
HBB Chr11:5248301 c.-50A>C NM_000518.4 rs34305195
HBB Chr11:5248301 c.-50A>G/T NM_000518.4
HBB Chr11:5248326 c.-75G>C NM_000518.4 rs63750400
HBB Chr11:5248326 c.-75G>T NM_000518.4
HBB Chr11:5248327 c.-76A>C NM_000518.4 rs281864525
HBB Chr11:5248328 c.-77A>G/T NM_000518.4
HBB Chr11:5248329 c.-78A>C/G NM_000518.4 rs33931746
HBB Chr11:5248330 c.-79A>G NM_000518.4 rs34598529
HBB Chr11:5248331 c.-80T>A/C NM_000518.4 rs33980857
HBB Chr11:5248332 c.-81A>C/G NM_000518.4 rs33981098
HBB Chr11:5248333 c.-82C>A/T NM_000518.4 rs34500389
HBB Chr11:5248342 c.-91A>C NM_000518.4
HBB Chr11:5248343 c.-92C>G NM_000518.4 rs397515291
HBB Chr11:5247062 c.316-106C>G NM_000518.4 rs34690599
HBB Chr11:5247081 c.316-125A>G NM_000518.4 rs63751175
HBB Chr11:5247102 c.316-146T>G NM_000518.4 rs35328027
HBB Chr11:5246970 c.316-14T>G NM_000518.4 rs35703285
HBB Chr11:5247153 c.316-197C>T NM_000518.4 rs34451549
HBB Chr11:5247216 c.316-260T>C NM_000518.4
HBB Chr11:5247046 c.316-90A>G NM_000518.4 rs63750433
HBB Chr11:5248044 c.93-15T>G NM_000518.4 rs35456885
HBB Chr11:5248050 c.93-21G>A NM_000518.4 rs35004220
HFE Chr6:26087649 c.-20G>A NM_000410.3 rs138378000
HPS3 Chr3:148888270 c.2888-1612G>A NM_032383.3 rs281865096
ITGA2B Chr17:42449567 c.*165T>C NM_000419.3
ITGA2B Chr17:42470923 c.-4082G>A NM_000419.3
ITGA2B Chr17:42458507 c.1211-78A>G NM_000419.3
ITGA2B Chr17:42455177 c.2095-19T>A NM_000419.3
ITGA2B Chr17:42463181 c.408+11C>A NM_000419.3
KLF1 Chr19:12998078 c.-124T>C NM_006563.3
KLF1 Chr19:12998108 c.-154C>T NM_006563.3 rs372651309
LAMTOR2 Chr1:156028185 c.*23C>A NM_014017.3
MLH1 Chr3:37035012 c.-27C>A NM_000249.3 rs587779001
MLH1 Chr3:37034997 c.-42C>T NM_000249.3 rs41285097
MLH1 Chr3:37038099 c.117-11T>A NM_000249.3 rs267607711
MLH1 Chr3:37070436 c.1558+13T>A NM_000249.3 rs267607834
MLH1 Chr3:37050292 c.454-13A>G NM_000249.3 rs267607749
MLH1 Chr3:37053487 c.589-9_589-6delGTTT NM_000249.3 rs752286654,rs587779026
MLH1 Chr3:37061788 c.885-9_887dupTCCTGACAGTTT NM_000249.3 rs63751620
MSH2 Chr2:47630150 c.-181G>A NM_000251.2 rs786201698
MSH2 Chr2:47630106 c.-225G>C NM_000251.2 rs138068023
MSH2 Chr2:47630251 c.-78_-77delTG NM_000251.2 rs587779182
MSH2 Chr2:47635062 c.212-478T>G NM_000251.2 rs587779138
MSH6 Chr2:48034014 c.*15A>C NM_000179.2
MTR Chr1:237057461 c.3205-196A>G NM_000254.2 rs544410324
MTR Chr1:236971838 c.340-166A>G NM_000254.2
MTR Chr1:236977232 c.609+1088G>A NM_000254.2 rs752526782
NF1 Chr17:29422056 c.-272G>A NM_001042492.2
NF1 Chr17:29422055 c.-273A>C NM_001042492.2
NF1 Chr17:29530107 c.1260+1604A>G NM_001042492.2
NF1 Chr17:29533239 c.1261-19G>A NM_001042492.2
NF1 Chr17:29534143 c.1392+754T>G NM_001042492.2
NF1 Chr17:29488136 c.288+2025T>G NM_001042492.2
NF1 Chr17:29577934 c.4110+1802delA NM_001042492.2 rs863224944
NF1 Chr17:29577082 c.4110+945A>G NM_001042492.2
NF1 Chr17:29580296 c.4173+278A>G NM_001042492.2
NF1 Chr17:29654479 c.5269-38A>G NM_001042492.2
NF1 Chr17:29656858 c.5610-456G>T NM_001042492.2
NF1 Chr17:29657848 c.5812+332A>G NM_001042492.2 rs863224491
NF1 Chr17:29508428 c.587-12T>A NM_001042492.2
NF1 Chr17:29508426 c.587-14T>A NM_001042492.2
NF1 Chr17:29664375 c.6428-11T>G NM_001042492.2
NF1 Chr17:29664618 c.6642+18A>G NM_001042492.2
NF1 Chr17:29676126 c.7190-12T>A NM_001042492.2
NF1 Chr17:29685481 c.7971-17C>G NM_001042492.2
NF1 Chr17:29685177 c.7971-321C>G NM_001042492.2
NF1 Chr17:29685665 c.8113+25A>T NM_001042492.2
NF1 Chr17:29510334 c.888+651T>A NM_001042492.2
NF1 Chr17:29510427 c.888+744A>G NM_001042492.2
NF1 Chr17:29510472 c.888+789A>G NM_001042492.2
OCA2 Chr15:28235808 c.1045-15T>G NM_000275.2 rs779461179
PALB2 Chr16:23649285 c.109-12T>A NM_024675.3 rs774949203
PARN Chr16:14724045 c.-165+2C>T NM_001134477.2
PC Chr11:66620883 c.1369-29A>G NM_000920.3
PDHA1 ChrX:19377861 c.*79_*90dupAGTCAATGAAAT NM_001173454.1
PDHA1 ChrX:19372579 c.625-30G>A NM_001173454.1
PDHA1 ChrX:19373648 c.873+26G>A NM_001173454.1
PDHX Chr11:34988372 c.816+11C>G NM_003477.2
PKLR Chr1:155271258 c.-72A>G NM_000298.5
PKLR Chr1:155271259 c.-73G>C NM_000298.5
PKLR Chr1:155271269 c.-83G>C NM_000298.5
PKLR Chr1:155263185 c.1269+44C>T NM_000298.5
PKLR Chr1:155265208 c.507+20C>A NM_000298.5
PROC Chr2:128186595 c.*73C>T NM_000312.3 rs199469473
PROC Chr2:128175988 c.-102T>A NM_000312.3
PROC Chr2:128175984 c.-106A>G NM_000312.3
PROC Chr2:128175983 c.-107A>G NM_000312.3
PROC Chr2:128176005 c.-85C>T NM_000312.3
PROC Chr2:128176001 c.-89T>C NM_000312.3
PROC Chr2:128175994 c.-96T>G NM_000312.3
PROC Chr2:128179040 c.237+15G>A NM_000312.3 rs528055589
PROC Chr2:128180582 c.263-28T>G NM_000312.3
PROC Chr2:128178842 c.71-17C>T NM_000312.3 rs138057813
PROS1 Chr3:93692761 c.-168C>T NM_000313.3 rs199469484
PTPN11 Chr12:112915602 c.934-59T>A NM_002834.3
RPS7 Chr2:3622941 c.-19+1G>T NM_001011.3
RPS7 Chr2:3622942 c.-19+2T>C NM_001011.3
SEC23B Chr20:18488615 c.-16A>G NM_006363.4
SEC23B Chr20:18488060 c.-571A>G NM_006363.4 rs559854357
SEC23B Chr20:18526845 c.1743+168A>G NM_006363.4 rs111951711
SEC23B Chr20:18491863 c.221+163A>G NM_006363.4 rs573898514
SEC23B Chr20:18491731 c.221+31A>G NM_006363.4
SEC23B Chr20:18492791 c.222-78C>T NM_006363.4 rs150393520
SERPINC1 Chr1:173886568 c.-171C>G NM_000488.3
SERPINC1 Chr1:173876666 c.1154-14G>A NM_000488.3
SLC4A1 Chr17:42340296 c.-62G>A NM_000342.3 rs387906565
SPTA1 Chr1:158626459 c.2806-13T>G NM_003126.2
TCN2 Chr22:31011112 c.581-176A>T NM_000355.3
TERC Chr3:169482870 n.-22C>T NR_001566.1
TERC Chr3:169482906 NR_001566.1
TERT Chr5:1295161 c.-57A>C NM_198253.2
THBD Chr20:23030292 c.-151G>T NM_000361.2 rs16984852
THBD Chr20:23030443 c.-302C>A NM_000361.2
TP53 Chr17:7590694 c.-29+1G>T NM_000546.5
TRNT1 Chr3:3188088 c.609-26T>C NM_182916.2
TYR Chr11:88960973 c.1037-18T>G NM_000372.4
UNC13D Chr17:73839907 c.118-307G>A NM_199242.2
UNC13D Chr17:73839908 c.118-308C>T NM_199242.2
UNC13D Chr17:73827442 c.2448-13G>A NM_199242.2 rs753762300
UNC13D Chr17:73826245 c.2831-13G>A NM_199242.2
VWF Chr12:6234258 c.-672C>T NM_000552.3 rs61750447
VWF Chr12:6101204 c.6599-20A>T NM_000552.3 rs61750621

Added and removed genes from the panel

Genes added Genes removed
ACD
AP3D1
ARPC1B
BRAF
BRCA1
CBL
CLCN7
CLPB
CSF3R
CYB5R3
DDX41
DHFR
DNAJC21
EGLN1
EPAS1
EPB41
EPCAM
EPOR
ERCC6L2
ETV6
F13B
FADD
FASLG
FLI1
FYB
GFI1
GFI1B
GINS1
IKZF1
JAK2
LAMTOR2
MAP2K1
MAP2K2
MCFD2
MECOM
MKL1
MTHFD1
NT5C3A
PARN
PAX5
PGM3
PIEZO1
PRKACG
RAC2
REN
RHAG
RIT1
RNF168
SAMD9
SAMD9L
SLC25A38
SLC37A4
SLC46A1
SMARCD2
SOS1
SRC
SRP72
TCN2
TF
THPO
TRNT1
VPS13B
VPS45
WDR1
WIPF1
RPS17
TCIRG1

Test strength

The strengths of this test include:
  • CAP and ISO-15189 accreditations covering all operations at Blueprint Genetics including all Whole Exome Sequencing, NGS panels and confirmatory testing
  • 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
  • Our Nucleus online portal providing transparent and easy access to quality and performance data at the patient level
  • Our publically available analytic validation demonstrating complete details of test performance
  • 1479 non-coding disease causing variants in Blueprint WES assay (please see below ‘Non-coding disease causing variants covered by this panel’)
  • Our rigorous variant classification based on modified ACMG 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

HBA1 and HBA2 genes have identical sequences at coding region and their mapping rely purely on differences at intronic/UTR regions. This reduces sensitivity for detecting variants in these region by using standard NGS diagnostics. However, Blueprint Genetics custom assay has good coverage (>20x) with improved mapping rates (mapping quality >40) within the target regions of these genes:  HBA1 80.7% and HBA2 59.4%. Our validation showed high mean coverage of 604x for HBA1 gene and 463x for HBA2. We have been able to detect sequence variants and some of the known disease causing deletions using our assay but some limitations in sensitivity is expected to exist at the moment. The following exons are not included in the panel as they are not sufficiently covered with high quality sequence reads: IKZF1 (4, 6, 7, 8), PMS2 (15), RBM8A (3), RPL15 (5). 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
  • Mitochondrial DNA variants
  • 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
  • Stretches of mononucleotide repeats
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments

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.

The Blueprint Genetics comprehensive hematology panel covers classical genes associated with inherited bleeding disorder, Inherited bone marrow failure syndrome, hereditary anemia and leukemia. The genes on the panel have been carefully selected based on scientific literature, mutation databases and our experience.

Our panels are sliced from our high-quality whole exome sequencing data. Please see our sequencing and detection performance table for different types of alterations at the whole exome level (Table).

Assays have been validated for different starting materials including EDTA-blood, isolated DNA (no FFPE), saliva and dry blood spots (filter card) and all provide high-quality results. The diagnostic yield varies substantially depending on the assay used, referring healthcare professional, hospital and country. Blueprint Genetics' Plus Analysis (Seq+Del/Dup) maximizes the chance to find a molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be a cost-effective first line test if your patient's phenotype is suggestive of a specific mutation type.

Performance of Blueprint Genetics Whole Exome Sequencing (WES) assay. All individual panels are sliced from WES data.

Sensitivity % (TP/(TP+FN) Specificity %
Single nucleotide variants 99.65% (412,456/413,893) >99.99%
Insertions, deletions and indels by sequence analysis
1-10 bps 96.94% (17,070/17,608) >99.99%
11-50 bps 99.07% (957/966) >99.99%
Copy number variants (exon level dels/dups)
Clinical samples (small CNVs, n=52)
1 exon level deletion 92.3% (24/26) NA
2 exons level deletion/duplication 100.0% (11/11) NA
3-7 exons level deletion/duplication 93.3% (14/15) NA
Microdeletion/-duplication sdrs (large CNVs, n=37))
Size range (0.1-47 Mb) 100% (37/37)
Simulated CNV detection
2 exons level deletion/duplication 90.98% (7,357/8,086) 99.96%
5 exons level deletion/duplication 98.63% (7,975/8,086) 99.98%
     
The performance presented above reached by WES with the following coverage metrics
     
Mean sequencing depth at exome level 174x
Nucleotides with >20x sequencing coverage (%) 99.4%

Bioinformatics

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 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. 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 such as, 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, the customer has an access to details of the analysis, including patient specific sequencing metrics, a gene level coverage plot and a list of regions with inadequate coverage if present. This reflects our mission to build fully transparent diagnostics where customers have easy access to crucial details of the analysis process.

Clinical interpretation

We provide customers with the most comprehensive clinical report available on the market. Clinical interpretation requires a fundamental understanding of clinical genetics and genetic principles. At Blueprint Genetics, our PhD molecular geneticists, medical geneticists and clinical consultants prepare the clinical statement together by evaluating the identified variants in the context of the phenotypic information provided in the requisition form. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals regardless of whether they have formal training in genetics.

Variant classification is the corner stone of clinical interpretation and resulting patient management decisions. Our classifications follow the Blueprint Genetics Variant Classification Schemes based on the ACMG guideline 2015. Minor modifications were made to increase reproducibility of the variant classification and improve the clinical validity of the report. Our experience with tens of thousands of clinical cases analyzed at our laboratory allowed us to further develop the industry standard.

The final step in the analysis of sequence variants is confirmation of variants classified as pathogenic or likely pathogenic using bi-directional Sanger sequencing. Variant(s) fulfilling all of the following criteria are not Sanger confirmed: 1) the variant quality score is above the internal threshold for a true positive call, 2) an unambiguous IGV in-line with the variant call and 3) previous Sanger confirmation of the same variant at least three times at Blueprint Genetics. Reported variants of uncertain significance are confirmed with bi-directional Sanger sequencing only if the quality score is below our internally defined quality score for true positive call. Reported copy number variations with a size <10 exons are confirmed by orthogonal methods such as qPCR if the specific CNV has been seen less than three times at Blueprint Genetics.

Our clinical statement includes tables for sequencing and copy number variants that include basic variant information (genomic coordinates, HGVS nomenclature, zygosity, allele frequencies, in silico predictions, OMIM 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 used, congress abstracts and mutation databases to help our customers further evaluate the reported findings if desired. The conclusion summarizes all of the existing information and provides our rationale for the classification of the variant.

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 within the family. In the case of variants of uncertain significance (VUS), we do not recommend family member risk stratification based on the VUS result. Furthermore, in the case of VUS, we do not recommend the use of genetic information in patient management or genetic counseling. For eligible cases, Blueprint Genetics offers a no charge service to investigate the role of reported VUS (VUS Clarification Service).

Our interpretation team analyzes millions of variants from thousands of individuals with rare diseases. Thus, our database, and our understanding of variants and related phenotypes, is growing by leaps and bounds. Our laboratory is therefore well positioned to re-classify previously reported variants as new information becomes available. If a variant previously reported by Blueprint Genetics is re-classified, our laboratory will issue a follow-up statement to the original ordering health care provider at no additional cost.

General resources