Comprehensive Hematology Panel

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

Test code: HE0101

The Blueprint Genetics Comprehensive Hematology Panel is a 175 gene test for genetic diagnostics of patients with clinical suspicion of hereditary anemia, inherited bleeding disorder, inherited bone marrow failure syndrome or leukemia.

This panel 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. These include congenital defects in neutrophils, inherited disorders in platelets and platelet function and a broad spectrum of red blood cell disorders. This panel comprises all the subpanels under the Hematology category.

About Hematological Diseases

Inherited hematological diseases are a group of blood disorders with variable clinical presentation. Depending on the underlying defect and the affected hematological cell populations the symptoms can vary from bleeding disorders to severe anemia or may cause significant immunosuppression. Furthermore, the inherited defects in coagulopathy may also cause thrombophilia increasing the risk of thrombosis already during the childhood. All genetic defects presenting bone marrow failure lead to severe immunosuppression possibly necessitating stem cell transplantation as a curative choice of treatment. Patients with inherited bone marrow failure syndromes have a high risk of developing cancer, either leukemia or solid tumors. The role of genetic diagnostics in inherited hematological diseases is essential. Currently, accurate genetic diagnosis is necessary to confirm the diagnosis of certain hematological diseases and guide their optimal treatment.

Availability

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: http://blueprintgenetics.com/faqs/#prenatal

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
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
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
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
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
CSF2RA* Surfactant metabolism dysfunction, pulmonary XL 2 17
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
CYCS* Thrombocytopenia AD 2 3
DKC1 Hoyeraal-Hreidarsson syndrome, Dyskeratosis congenita XL 47 71
DTNBP1 Hermansky-Pudlak syndrome AR 2 2
ELANE Neutropenia AD 37 213
EPB42 Spherocytosis AR 8 14
ERCC4 Fanconi anemia, Xeroderma pigmentosum AR 11 43
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
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
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
FLNA Frontometaphyseal dysplasia, Osteodysplasty Melnick-Needles, Otopalatodigital syndrome type 1, Otopalatodigital syndrome type 2, Terminal osseous dysplasia with pigmentary defects XL 102 220
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
GGCX Pseudoxanthoma elasticum-like disorder with multiple coagulation factor deficiency, Vitamin K-dependent clotting factors, combined deficiency AD/AR/Digenic 13 38
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
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
KLF1 Anemia, dyserythropoietic congenital, Blood group, Lutheran inhibitor AD/BG 16 46
KRAS* Noonan syndrome, Cardiofaciocutaneous syndrome AD 59 31
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
MASTL Thrombocytopenia AD 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
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
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
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
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
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
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
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
RPS17* Diamond-Blackfan anemia AD 4 18
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
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
SLC45A2 Skin/hair/eye pigmentation, Oculocutaneous albinism AD/AR 15 111
SLFN14 Thrombocytopenia AD/AR 4 4
SLX4 Fanconi anemia AR 11 49
SPTA1 Spherocytosis, Ellipsocytosis, Pyropoikilocytosis AD/AR 23 40
SPTB Spherocytosis, Anemia, neonatal hemolytic, Ellipsocytosis AD/AR 15 67
STX11 Hemophagocytic lymphohistiocytosis, familial AR 5 15
STXBP2 Hemophagocytic lymphohistiocytosis, familial AR 8 62
TBXA2R Bleeding disorder, platelet- AD 6
TCIRG1 Osteopetrosis, severe neonatal or infantile forms (OPTB1) AD/AR 12 124
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
THBD Thrombophilia due to thrombomodulin defect, Hemolytic uremic syndrome, atypical AD 5 21
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
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
VWF* Von Willebrand disease AD/AR 50 847
WAS Neutropenia, severe congenital, Thrombocytopenia, Wiskott-Aldrich syndrome XL 44 431
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 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 (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

Gene Genomic location HG19 HGVS RefSeq RS-number
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 Chr8:41566510 c.1900-17G>A NM_001142446.1 rs786205243
ANKRD26 Chr10:27389389 c.-134G>A NM_014915.2 rs863223318
ATM Chr11:108098321 c.-30-1G>T NM_000051.3 rs869312754
ATM Chr11:108141209 c.2839-579_2839-576delAAGT NM_000051.3
ATM Chr11:108179837 c.5763-1050A>G NM_000051.3 rs774925473
CDKN2A Chr9:21974860 c.-34G>T NM_000077.4 rs1800586
CUBN Chr10:17088532 c.3330-439C>G NM_001081.3 rs386833782
DKC1 ChrX:153991099 c.-142C>G NM_001363.3 rs199422241
F13A1 Chr6:6320808 c.-19+12A>T NM_000129.3 rs2815822
F2 Chr11:46761055 c.*97G>A NM_000506.4 rs1799963
F8 ChrX:154219579 c.601+1632G>A NM_000132.3 rs387906429
FANCC Chr9:98011653 c.-78-2A>G NM_000136.2 rs587779898
FGG Chr4:155530122 c.667-320A>T NM_021870.2
GP1BB Chr22:19710933 c.-160C>G NM_000407.4 rs730882059
HBA2 Chr16:223691 c.*92A>G NM_000517.4 rs63750067
HBB Chr11:5246718 c.*110T>C NM_000518.4 rs33978907
HBB Chr11:5246713 c.*110_*114delTAAAA NM_000518.4 rs35949130
HBB Chr11:5246713 c.*110_*114delTAAAA NM_000518.4 rs606231219
HBB Chr11:5246717 c.*111A>G NM_000518.4 rs63751128
HBB Chr11:5246716 c.*112A>G NM_000518.4 rs63750954
HBB Chr11:5246715 c.*113A>G NM_000518.4 rs33985472
HBB Chr11:5248387 c.-136C>G/T NM_000518.4 rs33994806
HBB Chr11:5248388 c.-137C>A/G/T NM_000518.4 rs33941377
HBB Chr11:5248389 c.-138T>C 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 Chr11:5248402 c.-151C>T NM_000518.4 rs63751208
HBB Chr11:5248301 c.-50A>C NM_000518.4 rs34305195
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 NM_000518.4 rs33980857
HBB Chr11:5248332 c.-81A>G NM_000518.4 rs33981098
HBB Chr11:5248333 c.-82C>A NM_000518.4 rs34500389
HBB Chr11:5247062 c.316-106C>G NM_000518.4 rs34690599
HBB Chr11:5247153 c.316-197C>T NM_000518.4 rs34451549
HBB Chr11:5248050 c.93-21G>A NM_000518.4 rs35004220
HPS3 Chr3:148888270 c.2888-1612G>A NM_032383.3 rs281865096
MLH1 Chr3:37035012 c.-27C>A NM_000249.3 rs587779001
MSH2 Chr2:47630251 c.-78_-77delTG NM_000251.2 rs587779182
MSH2 Chr2:47635062 c.212-478T>G NM_000251.2 rs587779138
NF1 Chr17:29577934 c.4110+1802delA NM_001042492.2 rs863224944
NF1 Chr17:29657848 c.5812+332A>G NM_001042492.2 rs863224491
PDHA1 ChrX:19377861 c.*79_*90dupAGTCAATGAAAT NM_001173454.1
SLC4A1 Chr17:42340296 c.-62G>A NM_000342.3 rs387906565
THBD Chr20:23030292 c.-151G>T NM_000361.2 rs16984852

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 Hematology Panel that covers classical genes associated with hereditary anemia, inherited bleeding disorder, inherited bone marrow failure syndrome and leukemia. 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 (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

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

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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