- Is a 298 gene panel that includes assessment of non-coding variants
Is ideal for patients with a clinical suspicion of any type of primary immunodeficiency (PID).
- PLUS
4 weeks
298
IM0301
Large
Summary
The Blueprint Genetics Primary Immunodeficiency Panel (test code IM0301):
ICD codes
Commonly used ICD-10 code(s) when ordering the Primary Immunodeficiency Panel
ICD-10 | Disease |
---|---|
D80.9 | Immunodeficiencies with antibody defects |
D84.1 | Complement deficiencies |
D81.9 | Combined immunodeficiencies |
Sample Requirements
- Blood (min. 1ml) in an EDTA tube
- Extracted DNA, min. 2 μg in TE buffer or equivalent
- Saliva (Oragene DNA OG-500 kit/OGD-500 or OG-575 & OGD-575)
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. 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
Gene | Associated phenotypes | Inheritance | ClinVar | HGMD |
---|---|---|---|---|
ACD | Dyskeratosis congenita, autosomal dominant 6, Dyskeratosis congenita, autosomal recessive 7 | AD/AR | 2 | 8 |
ACP5 | Spondyloenchondrodysplasia with immune dysregulation | AR | 12 | 26 |
ACTB* | Baraitser-Winter syndrome | AD | 55 | 60 |
ADA | Severe combined immunodeficiency due to adenosine deaminase deficiency | AR | 49 | 93 |
ADAM17 | Inflammatory skin and bowel disease, neonatal 1 | AR | 1 | 7 |
ADAR | Dyschromatosis symmetrica hereditaria, Aicardi-Goutières syndrome | AD/AR | 25 | 226 |
AICDA | Immunodeficiency with hyper-IgM | AD/AR | 14 | 50 |
AIRE | Autoimmune polyendocrinopathy syndrome | AD/AR | 73 | 134 |
AK2 | Reticular dysgenesis | AR | 14 | 17 |
ALPI | Inflammatory bowel disease | AR | 5 | |
AP3B1 | Hermansky-Pudlak syndrome | AR | 14 | 34 |
ARHGEF1 | Idiopathic bronchiectasis, Immunodeficiencies with antibody defects | AR | 1 | |
ARPC1B | Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease | AR | 2 | 4 |
ATM | Breast cancer, Ataxia-Telangiectasia | AD/AR | 1047 | 1109 |
ATP6AP1 | Immunodeficiency 47 | XL | 5 | 5 |
BACH2 | BACH2-related immunodeficiency and autoimmunity (BRIDA) | AD | 2 | |
BCL10 | Immunodeficiency 37 | AR | 16 | 1 |
BCL11B | Immunodeficiency 49 | AD | 8 | 12 |
BLM | Bloom syndrome | AR | 152 | 119 |
BLNK | Agammaglobulinemia 4 | AR | 2 | 3 |
BTK | Hypogammaglobulinemia, Agammaglobulinemia and isolated hormone deficiency, Agammaglobulinemia | XL | 114 | 908 |
C17ORF62 | Chronic granulomatous disease | AR | 1 | |
C1QA | C1q deficiency | AR | 2 | 7 |
C1QB | C1q deficiency | AR | 4 | 8 |
C1QC | C1q deficiency | AR | 4 | 10 |
C1S | Complement component C1s deficiency | AR | 4 | 10 |
C2* | Complement component 2 deficiency | AR | 4 | 9 |
C3 | Hemolytic uremic syndrome, atypical, Complement component 3 deficiency, Macular degeneration, age-related | AD/AR | 6 | 87 |
CARD11 | B-cell expansion with NFKB and T-cell anergy, Immunodeficiency | AD/AR | 12 | 9 |
CARD14 | Psoriasis | AD | 9 | 29 |
CARD9 | Candidiasis, familial, 2 | AR | 8 | 25 |
CASP10 | Autoimmune lymphoproliferative syndrome | AD | 5 | 7 |
CASP8 | Caspase 8 defiency | AR | 2 | 7 |
CD19 | Immunodeficiency, common variable | AR | 8 | 9 |
CD247 | Immunodeficiency | AR | 8 | 4 |
CD27 | Lymphoproliferative syndrome | AR | 4 | 8 |
CD3D | Immunodeficiency | AR | 3 | 5 |
CD3E | Immunodeficiency | AR | 4 | 7 |
CD3G | Immunodeficiency | AR | 5 | 3 |
CD40 | Immunodeficiency with Hyper-IgM | AR | 5 | 10 |
CD40LG | Immunodeficiency, with hyper-IgM | XL | 35 | 231 |
CD46* | Hemolytic uremic syndrome, atypical | AD/AR | 5 | 81 |
CD55# | Blood group, Cromer system | BG | 7 | 7 |
CD59 | CD59 deficiency | AR | 4 | 8 |
CD70 | Primary immunodeficiency | AR | 4 | |
CD79A | Agammaglobulinemia 3 | AR | 3 | 7 |
CD79B | Agammaglobulinemia 6 | AR | 2 | 3 |
CD81 | Immunodeficiency, common variable, 6 | AR | 1 | 1 |
CD8A | CD8 deficiency | AR | 1 | 1 |
CDCA7 | Immunodeficiency-centromeric instability-facial anomalies syndrome 3 | AR | 4 | 6 |
CDK9 | AR | 1 | ||
CEBPE | Specific granule deficiency 1 | AR | 3 | 4 |
CECR1 | Polyarteritis nodosa, ADA2 deficiency | AR | 15 | 50 |
CFB | Complement factor B deficiency, Hemolytic uremic syndrome, atypical | AD/AR | 2 | 26 |
CFD | Complement factor D deficiency | AR | 2 | 3 |
CFH* | Hemolytic uremic syndrome, atypical, Complement factor H deficiency, Basal laminar drusen | AD/AR | 18 | 305 |
CFI | Hemolytic uremic syndrome, atypical, Complement factor I deficiency | AD/AR | 10 | 143 |
CFP | Properdin deficiency | XL | 5 | 17 |
CFTR | Cystic fibrosis, Congenital bilateral absence of the vas deferens | AD/AR | 518 | 1803 |
CHD7 | Isolated gonadotropin-releasing hormone deficiency, CHARGE syndrome | AD | 276 | 860 |
CIITA | Bare lymphocyte syndrome | AR | 9 | 15 |
CLCN7 | Osteopetrosis | AD/AR | 15 | 98 |
CLPB | 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia (MEGCANN) | AR | 26 | 25 |
COLEC11 | 3MC syndrome | AR | 6 | 13 |
COPA | Autoimmune interstitial lung, joint, and kidney disease | AD | 6 | 6 |
CORO1A#* | Immunodeficiency | AR | 41 | 6 |
CR2 | Common variable immunodeficiency | AR | 2 | 16 |
CSF2RA#* | Surfactant metabolism dysfunction, pulmonary | XL | 2 | 17 |
CSF2RB | Surfactant metabolism dysfunction, pulmonary, 5 | AR | 2 | 6 |
CSF3R | Neutrophilia, hereditary | AD | 13 | 13 |
CTC1 | Cerebroretinal microangiopathy with calcifications and cysts | AR | 21 | 33 |
CTLA4 | Autoimmune lymphoproliferative syndrome, type V | AD | 11 | 34 |
CTPS1 | Immunodeficiency 24 | AR | 1 | 1 |
CTSC | Periodontitis, juvenile, Haim-Munk syndrome, Papillon-Lefevre syndrome | AR | 19 | 92 |
CXCR4 | Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome | AD | 5 | 15 |
CYBA | Chronic granulomatous disease | AR | 13 | 71 |
CYBB | Chronic granulomatous disease, Immunodeficiency | XL | 69 | 780 |
DBR1 | Immunodeficiency | AR | 1 | |
DCLRE1C* | Omenn syndrome, Severe combined immunodeficiency with sensitivity to ionizing radiation | AR | 18 | 89 |
DDX58 | Singleton-Merten syndrome | AD | 4 | 3 |
DGKE | Nephrotic syndrome | AR | 17 | 38 |
DKC1 | Hoyeraal-Hreidarsson syndrome, Dyskeratosis congenita | XL | 48 | 74 |
DNAJC21 | Bone marrow failure syndrome 3 | AR | 5 | 11 |
DNASE2 | Primary immunodeficiency | 2 | ||
DNMT3B | Immunodeficiency-centromeric instability-facial anomalies syndrome | AR | 14 | 47 |
DOCK2 | Immunodeficiency | AR | 7 | 6 |
DOCK8 | Hyper-IgE recurrent infection syndrome, Mental retardation, autosomal dominant 2 | AR | 54 | 168 |
EFL1* | Shwachman-Diamond syndrome | 3 | 2 | |
ELANE | Neutropenia | AD | 43 | 217 |
EPG5 | Vici syndrome | AR | 36 | 66 |
ERCC6L2 | Bone marrow failure syndrome 2 | AR | 4 | 9 |
EXTL3 | Immunoskeletal dysplasia with neurodevelopmental abnormalities (ISDNA) | AR | 4 | 8 |
FADD | Infections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovascular malformations | AR | 2 | 1 |
FAS | Autoimmune lymphoproliferative syndrome | AD/AR | 31 | 133 |
FASLG | Autoimmune lymphoproliferative syndrome, type IB | AD | 2 | 10 |
FCHO1 | Common variable immunodeficiency | AR | ||
FERMT3 | Leukocyte adhesion deficiency | AR | 8 | 14 |
FOXN1 | T-cell immunodeficiency, congenital alopecia, and nail dystrophy | AR | 6 | 6 |
FOXP3 | Immunodysregulation, polyendocrinopathy, and enteropathy | XL | 28 | 93 |
G6PC3 | Neutropenia, severe congenital, Dursun syndrome | AR | 11 | 37 |
G6PD | Glucose-6-phosphate dehydrogenase deficiency | XL | 45 | 226 |
GATA2 | Myelodysplastic syndrome, Chronic neutropenia associated with monocytopenia, evolving to myelodysplasia and acute myeloid leukemia, Acute myeloid leukemia, Emberger syndrome, Immunodeficiency | AD | 30 | 142 |
GFI1 | Neutropenia, severe congenital, 2 autosomal dominant, Neutropenia, nonimmune chronic idiopathic, of adults | AD | 2 | 6 |
GINS1 | Immunodeficiency | AR | 4 | 4 |
HAX1 | Neutropenia, severe congenital | AR | 11 | 21 |
HELLS | Immunodeficiency-centromeric instability-facial anomalies syndrome 4 | AR | 6 | 6 |
HYOU1 | Combined immunodeficiency | AR | 2 | |
ICOS | Immunodeficiency, common variable, 1 | AR | 3 | 4 |
IFIH1 | Singleton-Merten syndrome, Aicardi-Goutieres syndrome 7 | AD/AR | 14 | 19 |
IFNAR2 | Immunodeficiency 45 | AR | 1 | 2 |
IFNGR1 | Immunodeficiency | AD/AR | 16 | 42 |
IFNGR2 | Immunodeficiency | AR | 4 | 18 |
IGLL1* | Agammaglobulinemia | AR | 2 | 3 |
IKBKB | Immunodeficiency 15 | AR | 2 | 7 |
IKZF1 | Immunodeficiency, common variable, 13 | AD | 10 | 35 |
IL10 | Graft vs. host disease | AD | 1 | 5 |
IL10RA | Inflammatory bowel disease | AR | 4 | 43 |
IL10RB | Inflammatory bowel disease | AR | 2 | 19 |
IL12B | Immunodeficiency 28, Immunodeficiency 29 | AR | 4 | 13 |
IL12RB1# | Immunodeficiency | AR | 13 | 82 |
IL17RA | Immunodeficiency 51 | AR | 8 | 17 |
IL17RC | Candiasis, familial, 9 | AR | 3 | 4 |
IL1RN | Osteomyelitis, sterile multifocal, with periostitis and pustulosis | AR | 6 | 12 |
IL21 | Immunodeficiency, common variable, 11 | AR | 1 | 1 |
IL21R | Immunodeficiency, primary, autosomal recessive, IL21R-related | AR | 3 | 9 |
IL23R | Primary immunodeficiency | AR | 1 | |
IL2RA | Interleukin 2 receptor, alpha, deficiency | AR | 6 | 6 |
IL2RB | Primary immunodeficiency | AR | ||
IL2RG | Combined immunodeficiency | XL | 54 | 243 |
IL36RN | Pustular psoriasis, generalized | AR | 6 | 26 |
IL6ST* | Primary immunodeficiency | AR | ||
IL7R | Severe combined immunodeficiency, , T-cell negative, B-cell positive, NK cell positive | AR | 23 | 48 |
IRAK4 | IRAK4 deficiency, Invasive pneumococcal disease, recurrent, isolated, 1 | AR | 12 | 29 |
IRF2BP2 | Immunodeficiency, common variable, 14 | AD | 1 | 2 |
IRF8 | Immunodeficiency 32A (CD11C-positive/CD1C-positive dendritic cell deficiency), Immunodeficiency 32B (monocyte and dendritic cell deficiency) | AD/AR | 4 | 8 |
ISG15 | Immunodeficiency, with basal ganglia calcification | AR | 3 | 3 |
ITGB2 | Leukocyte adhesion deficiency | AR | 33 | 118 |
ITK | Lymphoproliferative syndrome | AR | 4 | 11 |
JAGN1 | Neutropenia, severe congenital | AR | 8 | 8 |
JAK1 | Primary immunodeficiency | AR | 4 | 6 |
JAK3 | Severe combined immunodeficiency, , T cell-negative, B cell-positive, natural killer cell-negative | AR | 30 | 66 |
KRAS* | Noonan syndrome, Cardiofaciocutaneous syndrome | AD | 63 | 35 |
LAMTOR2 | Immunodeficiency due to defect in MAPBP-interacting protein | AR | 1 | 1 |
LAT | Immunodeficiency 52 | AR | 2 | 18 |
LCK | Immunodeficiency | AR | 2 | 3 |
LIG1 | Primary immunodeficiency | AR | 3 | |
LIG4 | Severe combined immunodeficiency with sensitivity to ionizing radiation, LIG4 syndrome | AR | 18 | 36 |
LPIN2 | Majeed syndrome | AR | 12 | 14 |
LRBA | Common variable immunodeficiency | AR | 23 | 64 |
LYST | Chediak-Higashi syndrome | AR | 50 | 97 |
MAGT1 | Immunodeficiency, with magnesium defect, Epstein-Barr virus infection and neoplasia, Mental retardation, X-linked 95 | XL | 8 | 14 |
MALT1 | Immunodeficiency | AR | 3 | 5 |
MAP3K14 | Primary immunodeficiency with multifaceted aberrant lymphoid immunity | AR | 1 | 2 |
MASP1 | 3MC syndrome | AR | 11 | 22 |
MEFV | Familial Mediterranean fever | AD/AR | 29 | 182 |
MKL1 | Primary immunodeficiency | AR | 4 | |
MOGS | Congenital disorder of glycosylation | AR | 7 | 8 |
MRE11A | Ataxia-telangiectasia-like disorder-1 | AR | 57 | 56 |
MSN* | Immunodeficiency 50 | XL | 2 | 2 |
MTHFD1 | Severe combined immunodeficiency | AR | 9 | 11 |
MVK | Mevalonic aciduria, Hyper-IgD syndrome, Porokeratosis 3, multiple types | AD/AR | 35 | 181 |
MYD88 | MYD88 deficiency | AR | 5 | 5 |
MYO5A | Griscelli syndrome | AR | 7 | 9 |
NBN | Breast cancer, Nijmegen breakage syndrome | AD/AR | 188 | 97 |
NCF1#* | Chronic granulomatous disease | AR | 18 | 44 |
NCF2 | Chronic granulomatous disease | AR | 19 | 72 |
NCF4 | Granulomatous disease | AR | 4 | 5 |
NCSTN | Acne inversa, familial 1 | AD | 7 | 30 |
NFKB1 | Common variable immunodeficiency | AD | 8 | 17 |
NFKB2 | Common variable immunodeficiency | AD | 6 | 11 |
NFKBIA | Ectodermal dysplasia, anhidrotic, with T-cell immunodeficiency | AD | 5 | 11 |
NHEJ1 | Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation | AR | 15 | 16 |
NHP2 | Dyskeratosis congenita | AR | 5 | 3 |
NLRC4 | Autoinflammation with infantile enterocolitis (AIFEC), Familial cold autoinflammatory syndrome 4 | AD | 6 | 8 |
NLRP1 | Palmoplantar carcinoma, multiple self-healing, Autoinflammation with arthritis and dyskeratosis | AD/AR | 5 | 15 |
NLRP12 | Familial cold autoinflammatory syndrome | AD | 12 | 12 |
NLRP3 | Neonatal onset multisystem inflammatory disease (NOMID), Muckle-Wells syndrome, Chronic infantile neurologic cutaneous articular (CINCA) syndrome, Familial cold-induced autoinflammatory syndrome 1 | AD | 20 | 136 |
NOD2 | Blau syndrome, Sarcoidosis, early-onset | AD/AR | 12 | 70 |
NOP10 | Dyskeratosis congenita | AR | 1 | 1 |
NRAS | Noonan syndrome | AD | 31 | 14 |
NSMCE3 | Lung disease, immunodeficiency, and chromosome breakage syndrome (LICS) | AR | 2 | 2 |
OFD1 | Simpson-Golabi-Behmel syndrome, Retinitis pigmentosa, Orofaciodigital syndrome, Joubert syndrome | XL | 153 | 160 |
ORAI1 | Immunodeficiency, Myopathy, tubular aggregate, 2 | AR | 9 | 13 |
OTULIN | Autoinflammation, panniculitis, and dermatosis syndrome (AIPDS) | AR | 8 | 3 |
PARN* | Pulmonary fibrosis and/or bone marrow failure, Dyskeratosis congenita | AD/AR | 15 | 29 |
PEPD | Prolidase deficiency | AR | 12 | 31 |
PGM3 | Immunodeficiency 23 | AR | 14 | 15 |
PIGA* | Multiple congenital anomalies-hypotonia-seizures syndrome | XL | 24 | 27 |
PIK3CD* | Immunodeficiency | AD | 6 | 12 |
PIK3R1 | Agammaglobulinemia, SHORT syndrome | AD/AR | 33 | 24 |
PLCG2 | Familial cold autoinflammatory syndrome 3 (PLAID), Autoinflammation, antibody deficiency, and immune dysregulation syndrome (APLAID) | AD | 7 | 13 |
PMS2* | Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposis | AD/AR | 319 | 342 |
PNP | Purine nucleoside phosphorylase deficiency | AR | 11 | 33 |
POLD1 | Colorectal cancer, Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, Idiopathic bronchiectasis, Immunodeficiency | AD/AR | 3 | 31 |
POLE | Colorectal cancer, Facial dysmorphism, immunodeficiency, livedo, and short stature syndrome (FILS syndrome) | AD/AR | 8 | 70 |
POLE2 | Combined immunodeficiency | AR | 3 | |
POMP | Keratosis linearis with ichthyosis congenita and sclerosing keratoderma | AR | 5 | 4 |
PRF1 | Lymphoma, non-Hodgkin, Aplastic anemia, adult-onset, Hemophagocytic lymphohistiocytosis | AR | 24 | 183 |
PRG4 | Camptodactyly-arthropathy-coxa vara-pericarditis syndrome | AR | 6 | 35 |
PRKCD | Autoimmune lymphoproliferative syndrome type III | AR | 4 | 6 |
PRKDC | Immunodeficiency | AR | 6 | 9 |
PSENEN | Acne inversa, familial, 2 | AD | 7 | 17 |
PSMB8 | Nakajo-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 syndrome | AR | 5 | 9 |
PSTPIP1 | Pyogenic sterile arthritis, pyoderma gangrenosum, and acne | AD | 5 | 29 |
PTPRC | Severe combined immunodeficiency, , T-cell negative, B-cell positive, NK cell positive | AR | 4 | 5 |
RAB27A | Griscelli syndrome, Elejalde syndrome | AR | 18 | 54 |
RAC2 | Neutrophil immunodeficiency syndrome | AD | 2 | 3 |
RAG1 | Omenn 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 granulomas | AR | 47 | 184 |
RAG2 | Omenn syndrome, Combined cellular and humoral immune defects with granulomas | AR | 28 | 79 |
RASGRP1 | Primary immunodeficiency | AR | 1 | 3 |
RBCK1 | Polyglucosan body myopathy | AR | 11 | 14 |
RECQL4 | Baller-Gerold syndrome, RAPADILINO syndrome, Rothmund-Thomson syndrome | AR | 82 | 114 |
RELA* | Autoimmune lymphoproliferative syndrome | AD | 1 | 3 |
RFX5 | Bare lymphocyte syndrome | AR | 4 | 10 |
RFXANK | MHC class II deficiency | AR | 8 | 16 |
RFXAP | Bare lymphocyte syndrome | AR | 6 | 9 |
RHOH | T-cell immunodeficiency with epidermodysplasia verruciformis | AD/AR | 1 | |
RIPK1 | Primary immunodeficiency | AR | 3 | 1 |
RLTPR | Combined immunodeficiency | AR | 11 | 8 |
RMRP | Cartilage-hair hypoplasia, Metaphyseal dysplasia without hypotrichosis, Anauxetic dysplasia | AR | 87 | 123 |
RNASEH2A | Aicardi-Goutières syndrome | AR | 13 | 21 |
RNASEH2B | Aicardi-Goutières syndrome | AR | 16 | 41 |
RNASEH2C | Aicardi-Goutières syndrome | AR | 6 | 14 |
RNF168 | RIDDLE syndrome | AR | 4 | 5 |
RNF31 | HOIP and LUBAC deficiency | AR | 1 | |
RNU4ATAC | Roifman syndrome, Microcephalic osteodysplastic primordial dwarfism type 1, Microcephalic osteodysplastic primordial dwarfism type 3 | AR | 15 | 24 |
RORC | Immunodeficiency 42 | AR | 3 | 3 |
RPSA | Asplenia, isolated congenital | AD | 7 | 8 |
RTEL1 | Pulmonary fibrosis and/or bone marrow failure, Dyskeratosis congenita | AD/AR | 58 | 51 |
SAMD9 | Mirage syndrome, Tumoral calcinosis, normophosphatemic | AD/AR | 10 | 27 |
SAMD9L | Ataxia-pancytopenia syndrome | AD | 4 | 16 |
SAMHD1 | Aicardi-Goutières syndrome, Chilblain lupus 2 | AD/AR | 25 | 56 |
SBDS* | Aplastic anemia, Shwachman-Diamond syndrome, Severe spondylometaphyseal dysplasia | AD/AR | 19 | 90 |
SERPING1 | Angioedema, Complement component 4, partial deficiency of | AD/AR | 34 | 563 |
SH2D1A | Lymphoproliferative syndrome | XL | 21 | 129 |
SLC29A3 | Histiocytosis-lymphadenopathy plus syndrome, Dysosteosclerosis | AR | 17 | 25 |
SLC35C1 | Congenital disorder of glycosylation, Leukocyte adhesion deficiency | AR | 6 | 7 |
SLC37A4 | Glycogen storage disease | AR | 49 | 113 |
SLC39A7 | Agammaglobulinemia | AR | ||
SLC46A1 | Folate malabsorption | AR | 17 | 23 |
SLC7A7 | Lysinuric protein intolerance | AR | 55 | 67 |
SMARCAL1 | Schimke immunoosseous dysplasia | AR | 20 | 88 |
SMARCD2 | Specific granule defiency 2 | AR | 3 | 1 |
SP110 | Hepatic venoocclusive disease with immunodeficiency | AR | 8 | 8 |
SPINK5 | Netherton syndrome | AR | 29 | 85 |
SPPL2A | Primary immunodeficiency | AR | 1 | |
SRP54 | Shwachman-Diamond syndrome | AD | 3 | |
SRP72* | Bone marrow failure syndrome 1 | AD | 2 | 5 |
STAT1 | Immunodeficiency | AD/AR | 39 | 122 |
STAT2 | Immunodeficiency | AR | 3 | 6 |
STAT3 | Hyper-IgE recurrent infection syndrome, Autoimmune disease, multisystem, infantile onset | AD | 47 | 152 |
STAT5B* | Growth hormone insensitivity with immunodeficiency | AR | 9 | 13 |
STIM1 | Stormorken syndrome, Immunodeficiency, Myopathy, tubular aggregate 1 | AD/AR | 13 | 24 |
STK4 | T-cell immunodeficiency syndrome, recurrent infections, autoimmunity, | AR | 3 | 7 |
STX11 | Hemophagocytic lymphohistiocytosis, familial | AR | 8 | 22 |
STXBP2 | Hemophagocytic lymphohistiocytosis, familial | AR | 12 | 77 |
TAP1 | Bare lymphocyte syndrome | AR | 1 | 7 |
TAP2 | Bare lymphocyte syndrome | AR | 4 | 8 |
TAPBP | Bare lymphocyte syndrome | AR | 1 | 2 |
TBX1 | Conotruncal anomaly face syndrome | AD | 17 | 72 |
TCF3 | Agammaglobulinemia 8, autosomal dominant | AD | 1 | 5 |
TCN2 | Transcobalamin II deficiency | AR | 9 | 35 |
TERC | Aplastic anemia, Pulmonary fibrosis and/or bone marrow failure, telomere-related, Dyskeratosis congenita | AD | 42 | 73 |
TERT | Aplastic anemia, Pulmonary fibrosis and/or bone marrow failure, telomere-related, Dyskeratosis congenita | AD/AR | 48 | 156 |
TFRC | Immunodeficiency 46 | AR | 8 | 2 |
TGFB1 | Diaphyseal dysplasia Camurati-Engelmann | AD | 15 | 23 |
THBD | Thrombophilia due to thrombomodulin defect, Hemolytic uremic syndrome, atypical | AD | 5 | 28 |
TINF2 | Revesz syndrome, Dyskeratosis congenita | AD | 25 | 42 |
TMC6 | Epidermodysplasia verruciformis | AR | 8 | 7 |
TMC8 | Epidermodysplasia verruciformis | AR | 3 | 9 |
TMEM173 | STING-associated vasculopathy, infantile-onsent (SAVI) | AD | 4 | 10 |
TNFAIP3 | Autoinflammatory syndrome, familial, Behcet-like | AD | 8 | 23 |
TNFRSF13B | Common variable immunodeficiency, Immunoglobulin A deficiency | AD/AR | 7 | 48 |
TNFRSF1A# | Periodic fever (TNF receptor-associated periodic syndrome) | AD | 19 | 106 |
TNFRSF4 | Immunodeficiency | AR | 1 | 1 |
TNFRSF9 | ||||
TRAF3IP2 | Candidiasis, familial 8 | AR | 1 | 3 |
TREX1 | Vasculopathy, retinal, with cerebral leukodystrophy, Chilblain lupus, Aicardi-Goutières syndrome | AD/AR | 30 | 71 |
TRNT1 | Retinitis pigmentosa and erythrocytic microcytosis, Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay | AR | 13 | 26 |
TTC37 | Trichohepatoenteric syndrome, Primary immunodeficiency | AR | 12 | 64 |
TTC7A | Gastrointestinal defects and immunodeficiency syndrome | AR | 21 | 46 |
TYK2 | Immunodeficiency | AR | 9 | 9 |
UNC119 | Immunodeficiency, Cone-rod dystrophy 2 | AR | 1 | 5 |
UNC13D | Hemophagocytic lymphohistiocytosis, familial | AR | 22 | 192 |
UNC93B1* | Herpes simplex encephalitis, susceptibility to, 1 | AR | 2 | |
UNG | Immunodeficiency with hyper-IgM, type 5 | AR | 6 | 7 |
USB1 | Poikiloderma with neutropenia | AR | 24 | 22 |
USP18#* | Pseudo-TORCH syndrome 2 | AR | 40 | 1 |
VPS13B | Cohen syndrome | AR | 351 | 203 |
VPS45# | Neutropenia, severe congenital, 5, autosomal recessive | AR | 3 | 4 |
WAS | Neutropenia, severe congenital, Thrombocytopenia, Wiskott-Aldrich syndrome | XL | 57 | 439 |
WDR1 | AR | 8 | ||
WIPF1 | Wiskott-Aldrich syndrome 2 | AR | 2 | 3 |
WRAP53 | Dyskeratosis congenita | AR | 7 | 6 |
XIAP* | Lymphoproliferative syndrome | XL | 14 | 96 |
ZAP70 | Selective T-cell defect | AR | 15 | 29 |
ZBTB24 | Immunodeficiency-Centromeric Instability-Facial Anomalies 2 | AR | 7 | 17 |
ZNF341* | AR | 5 |
* 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), 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.
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 Primary Immunodeficiency Panel
Gene | Genomic location HG19 | HGVS | RefSeq | RS-number |
---|---|---|---|---|
ADA | Chr20:43248503 | c.1079-15T>A | NM_000022.2 | rs387906268 |
ADA | Chr20:43249076 | c.976-34G>A | NM_000022.2 | |
ATM | Chr11:108093770 | c.-174A>G | NM_000051.3 | |
ATM | Chr11:108094508 | c.-31+595G>A | NM_000051.3 | |
ATM | Chr11:108098321 | c.-30-1G>T | NM_000051.3 | rs869312754 |
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 | Chr11:108164028 | c.4612-12A>G | NM_000051.3 | |
ATM | Chr11:108179837 | c.5763-1050A>G | NM_000051.3 | rs774925473 |
ATM | Chr11:108214779 | c.8418+681A>G | NM_000051.3 | rs748635985 |
BTK | ChrX:100609705 | c.1567-23A>C/G | NM_000061.2 | |
BTK | ChrX:100609705 | c.1567-23A>G | NM_000061.2 | |
BTK | ChrX:100609705 | c.1567-23A>C | NM_000061.2 | |
BTK | ChrX:100612468 | c.1177+28_1177+29insAGAAAAAAGGT | NM_000061.2 | |
BTK | ChrX:100613695 | c.895-11C>A | NM_000061.2 | |
BTK | ChrX:100625094 | c.310-28_310-27delGCinsTG | NM_000061.2 | |
BTK | ChrX:100629415 | c.240+109C>A | NM_000061.2 | |
BTK | ChrX:100629416 | c.240+108T>G | NM_000061.2 | |
BTK | ChrX:100629827 | c.142-205A>G | NM_000061.2 | |
BTK | ChrX:100630121 | c.141+11C>T | NM_000061.2 | rs138411530 |
BTK | ChrX:100641044 | c.-31+6T>G | NM_000061.2 | |
BTK | ChrX:100641045 | c.-31+5G>A/C/T | NM_000061.2 | |
BTK | ChrX:100641045 | c.-31+5G>A | NM_000061.2 | |
BTK | ChrX:100641045 | c.-31+5G>T | NM_000061.2 | rs1131691354 |
BTK | ChrX:100641045 | c.-31+5G>C | NM_000061.2 | |
BTK | ChrX:100641049 | c.-31+1G>A/C | NM_000061.2 | |
BTK | ChrX:100641049 | c.-31+1G>A | NM_000061.2 | |
BTK | ChrX:100641049 | c.-31+1G>C | NM_000061.2 | |
BTK | ChrX:100641050 | c.-31G>A | NM_000061.2 | |
BTK | ChrX:100641212 | c.-193A>G | NM_000061.2 | |
C1QB | Chr1:22985931 | c.-17-2A>C | NM_000491.3 | |
CD40LG | ChrX:135736498 | c.289-32_289-25delAAAATGAC | NM_000074.2 | |
CD40LG | ChrX:135736517 | c.289-15T>A | NM_000074.2 | |
CD40LG | ChrX:135737600 | c.347-915A>T | NM_000074.2 | |
CD46 | Chr1:207930564 | c.286+27delT | NM_002389.4 | rs771669828 |
CECR1 | Chr22:17664763 | c.1082-1113delA | NM_017424.2 | |
CFTR | Chr7:117119654 | c.-495C>T | NM_000492.3 | rs397507565 |
CFTR | Chr7:117119797 | NM_000492.3 | ||
CFTR | Chr7:117119900 | c.-249G>C | NM_000492.3 | |
CFTR | Chr7:117119984 | c.-165G>A | NM_000492.3 | rs145483167 |
CFTR | Chr7:117120064 | c.-85C>G | NM_000492.3 | |
CFTR | Chr7:117120115 | c.-34C>T | NM_000492.3 | rs756314710 |
CFTR | Chr7:117120325 | c.53+124T>C | NM_000492.3 | |
CFTR | Chr7:117179040 | c.870-1113_870-1110delGAAT | NM_000492.3 | rs397508809 |
CFTR | Chr7:117182041 | c.1117-26_1117-25delAT | NM_000492.3 | rs397508159 |
CFTR | Chr7:117199500 | c.1393-18G>A | NM_000492.3 | rs397508199 |
CFTR | Chr7:117218381 | c.1585-9412A>G | NM_000492.3 | rs397508229 |
CFTR | Chr7:117227774 | c.1585-19T>C | NM_000492.3 | rs778457306 |
CFTR | Chr7:117227921 | c.1679+34G>T | NM_000492.3 | rs767901668 |
CFTR | Chr7:117229521 | c.1680-886A>G | NM_000492.3 | rs397508266 |
CFTR | Chr7:117229524 | c.1680-883A>G | NM_000492.3 | |
CFTR | Chr7:117243855 | c.2908+19G>C | NM_000492.3 | rs370683572 |
CFTR | Chr7:117246713 | c.2909-15T>G | NM_000492.3 | rs397508455 |
CFTR | Chr7:117246840 | c.2988+33G>T | NM_000492.3 | |
CFTR | Chr7:117251619 | c.3140-16T>A | NM_000492.3 | rs767232138 |
CFTR | Chr7:117251624 | c.3140-11A>G | NM_000492.3 | |
CFTR | Chr7:117266272 | c.3469-1304C>G | NM_000492.3 | |
CFTR | Chr7:117267864 | c.3717+40A>G | NM_000492.3 | rs397508595 |
CFTR | Chr7:117282680 | c.3873+33A>G | NM_000492.3 | rs397508622 |
CFTR | Chr7:117288374 | c.3874-4522A>G | NM_000492.3 | |
CFTR | Chr7:117308395 | c.*1233T>A | NM_000492.3 | |
CHD7 | Chr8:61734568 | c.2836-15C>G | NM_017780.3 | |
CHD7 | Chr8:61757794 | c.5051-15T>A | NM_017780.3 | |
CHD7 | Chr8:61763034 | c.5405-18C>A | NM_017780.3 | rs199981784 |
CHD7 | Chr8:61763039 | c.5405-13G>A | NM_017780.3 | rs1131690787 |
CLCN7 | Chr16:1506057 | c.916+57A>T | NM_001287.5 | |
CLCN7 | Chr16:1507356 | c.739-18G>A | NM_001287.5 | rs371893553 |
CTSC | Chr11:88070895 | c.-55C>A | NM_001814.4 | rs766114323 |
CYBA | Chr16:88712620 | c.288-15C>G | NM_000101.3 | |
CYBB | ChrX:37639262 | c.-69A>C | NM_000397.3 | |
CYBB | ChrX:37639262 | NM_000397.3 | ||
CYBB | ChrX:37639264 | c.-67T>C | NM_000397.3 | |
CYBB | ChrX:37639266 | c.-65C>T | NM_000397.3 | |
CYBB | ChrX:37639267 | c.-64C>T | NM_000397.3 | |
CYBB | ChrX:37641327 | c.46-14_46-11delTTCTinsGAA | NM_000397.3 | |
CYBB | ChrX:37641330 | c.46-11T>G | NM_000397.3 | |
CYBB | ChrX:37642713 | c.142-28_142-12delACTCTGCTCCCTTTCCC | NM_000397.3 | |
CYBB | ChrX:37642731 | c.142-12delCinsACCTCTTCTAG | NM_000397.3 | |
CYBB | ChrX:37654041 | c.483+978G>T | NM_000397.3 | |
CYBB | ChrX:37656474 | c.674+1080A>G | NM_000397.3 | |
CYBB | ChrX:37656731 | c.674+1337T>G | NM_000397.3 | |
CYBB | ChrX:37657051 | c.675-1157A>G | NM_000397.3 | |
CYBB | ChrX:37664248 | c.1152-11T>G | NM_000397.3 | |
DGKE | Chr17:54925466 | c.888+40A>G | NM_003647.2 | |
DKC1 | ChrX:153991099 | c.-142C>G | NM_001363.3 | rs199422241 |
DKC1 | ChrX:153991100 | c.-141C>G | NM_001363.3 | |
DKC1 | ChrX:153993704 | c.85-15T>C | NM_001363.3 | |
DNMT3B | Chr20:31395557 | c.2421-11G>A | NM_006892.3 | rs547940069 |
DOCK8 | Chr9:317025 | c.742-18C>G | NM_203447.3 | rs112373444 |
DOCK8 | Chr9:317028 | c.742-15T>G | NM_203447.3 | rs111627162 |
DOCK8 | Chr9:368196 | c.1797+61A>C | NM_203447.3 | rs786205596 |
FAS | Chr10:90770494 | c.506-16A>G | NM_000043.4 | |
FASLG | Chr1:172628081 | c.-261T>C | NM_000639.1 | |
FOXP3 | ChrX:49106917 | c.*878A>G | NM_014009.3 | |
FOXP3 | ChrX:49106919 | c.*876A>G | NM_014009.3 | |
FOXP3 | ChrX:49121118 | c.-23+5G>A | NM_014009.3 | |
FOXP3 | ChrX:49121121 | c.-23+2T>G | NM_014009.3 | |
FOXP3 | ChrX:49121122 | c.-23+1G>A | NM_014009.3 | |
FOXP3 | ChrX:49121122 | c.-23+1G>T | NM_014009.3 | |
GATA2 | Chr3:128202131 | c.1017+572C>T | NM_032638.4 | |
GATA2 | Chr3:128202162 | c.1017+513_1017+540delGGAGTTTCCTATCCGGACATCTGCAGCC | NM_032638.4 | |
GATA2 | Chr3:128202171 | c.1017+532T>A | NM_032638.4 | |
GINS1 | Chr20:25388397 | c.-60A>G | NM_021067.3 | |
GINS1 | Chr20:25388409 | c.-48C>G | NM_021067.3 | |
IL10RB | Chr21:34668714 | c.*52C>T | NM_000628.4 | |
IL2RG | ChrX:70327277 | c.*307_*308delAA | NM_000206.2 | |
IL2RG | ChrX:70327278 | c.*308A>G | NM_000206.2 | |
IL2RG | ChrX:70330553 | c.270-15A>G | NM_000206.2 | |
IL2RG | ChrX:70331494 | c.-105C>T | NM_000206.2 | |
IL7R | Chr5:35867853 | c.379+288G>A | NM_002185.3 | |
IRAK4 | Chr12:44178047 | c.1188+520A>G | NM_016123.3 | |
ITGB2 | Chr21:46320404 | c.742-14C>A | NM_000211.3 | rs183204825 |
ITGB2 | Chr21:46321660 | c.500-12T>G | NM_000211.3 | |
JAK3 | Chr19:17943239 | c.2680+89G>A | NM_000215.3 | |
JAK3 | Chr19:17946035 | c.1915-11G>A | NM_000215.3 | |
LAMTOR2 | Chr1:156028185 | c.*23C>A | NM_014017.3 | |
MEFV | Chr16:3306599 | c.-12C>G | NM_000243.2 | rs104895148 |
MEFV | Chr16:3306969 | c.-382C>G | NM_000243.2 | |
MVK | Chr12:110029032 | c.769-7dupT | NM_000431.2 | rs104895348 |
OFD1 | ChrX:13768358 | c.935+706A>G | NM_003611.2 | rs730880283 |
OFD1 | ChrX:13773245 | c.1130-22_1130-19delAATT | NM_003611.2 | rs312262865 |
OFD1 | ChrX:13773249 | c.1130-20_1130-16delTTGGT | NM_003611.2 | |
PARN | Chr16:14724045 | c.-165+2C>T | NM_001134477.2 | |
PMS2 | Chr7:6027263 | c.1145-31_1145-13delCTGACCCTCTTCTCCGTCC | NM_000535.5 | rs751973268 |
PMS2 | Chr7:6048599 | c.23+21_23+28delTCCGGTGT | NM_000535.5 | |
PNP | Chr14:20942914 | c.286-18G>A | NM_000270.3 | |
POLE | Chr12:133249181 | c.1686+32C>G | NM_006231.2 | rs762985435 |
POMP | Chr13:29233225 | c.-95delC | NM_015932.5 | rs112368783 |
PSENEN | Chr19:36236501 | c.-192_-190delAGA | NM_172341.2 | rs554724520 |
RAG2 | Chr11:36619652 | c.-28G>C | NM_000536.3 | |
RFXANK | Chr19:19307761 | c.188-11C>T | NM_003721.3 | rs201545133 |
RMRP | Chr9:35658026 | NR_003051.3 | rs781730798 | |
RMRP | Chr9:35658026 | NR_003051.3 | ||
RMRP | Chr9:35658026 | NR_003051.3 | ||
RMRP | Chr9:35658026 | NR_003051.3 | ||
RMRP | Chr9:35658027 | NR_003051.3 | ||
RMRP | Chr9:35658027 | NR_003051.3 | ||
RMRP | Chr9:35658027 | NR_003051.3 | ||
RMRP | Chr9:35658027 | NR_003051.3 | rs727502775 | |
RMRP | Chr9:35658027 | NR_003051.3 | ||
RMRP | Chr9:35658028 | NR_003051.3 | ||
RMRP | Chr9:35658028 | NR_003051.3 | ||
RMRP | Chr9:35658029 | NR_003051.3 | ||
RMRP | Chr9:35658029 | NR_003051.3 | ||
RMRP | Chr9:35658032 | NR_003051.3 | ||
RNASEH2B | Chr13:51501530 | c.65-13G>A | NM_024570.3 | |
RNASEH2B | Chr13:51519550 | c.511-13G>A | NM_024570.3 | |
RPSA | Chr3:39448260 | c.-34+5G>C | NM_002295.4 | |
SERPING1 | Chr11:57365055 | c.-163C>T | NM_000062.2 | |
SERPING1 | Chr11:57365057 | c.-161A>G | NM_000062.2 | |
SERPING1 | Chr11:57365118 | c.-100C>G | NM_000062.2 | rs578018379 |
SERPING1 | Chr11:57365720 | c.-22-2A>C/G | NM_000062.2 | |
SERPING1 | Chr11:57365720 | c.-22-2A>C | NM_000062.2 | |
SERPING1 | Chr11:57365720 | c.-22-2A>G | NM_000062.2 | |
SERPING1 | Chr11:57365721 | c.-22-1G>A | NM_000062.2 | |
SERPING1 | Chr11:57373471 | c.686-12A>G | NM_000062.2 | |
SERPING1 | Chr11:57373867 | c.890-14C>G | NM_000062.2 | |
SERPING1 | Chr11:57381788 | c.1250-13G>A | NM_000062.2 | |
SH2D1A | ChrX:123499593 | c.138-17_138-11delAGTTTAT | NM_002351.4 | |
SLC29A3 | Chr10:73122778 | c.*413G>A | NM_018344.5 | |
SPINK5 | Chr5:147465956 | c.283-12T>A | NM_006846.3 | |
SPINK5 | Chr5:147484503 | c.1431-12G>A | NM_006846.3 | rs368134354 |
SPINK5 | Chr5:147491511 | c.1820+53G>A | NM_006846.3 | rs754599628 |
STX11 | Chr6:144508713 | c.*85_*86insT | NM_003764.3 | |
STXBP2 | Chr19:7705761 | c.326-23_326-16delGCCCCACT | NM_006949.3 | |
TBX1 | Chr22:19743578 | c.-777C>T | NM_080647.1 | |
TBX1 | Chr22:19743735 | c.-620A>C | NM_080647.1 | rs536892777 |
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 | ||
TERC | Chr3:169482948 | n.-100C>G | NR_001566.1 | rs199422256 |
TERC | Chr3:169483086 | NR_001566.1 | rs199422255 | |
TERT | Chr5:1271334 | c.2383-15C>T | NM_198253.2 | rs574645600 |
TERT | Chr5:1295161 | c.-57A>C | NM_198253.2 | |
THBD | Chr20:23030319 | NM_000361.2 | ||
THBD | Chr20:23030443 | c.-302C>A | NM_000361.2 | |
TRNT1 | Chr3:3188088 | c.609-26T>C | NM_182916.2 | |
UNC13D | Chr17:73826245 | c.2831-13G>A | NM_199242.2 | |
UNC13D | Chr17:73827442 | c.2448-13G>A | NM_199242.2 | rs753762300 |
UNC13D | Chr17:73839907 | c.118-307G>A | NM_199242.2 | |
UNC13D | Chr17:73839908 | c.118-308C>T | NM_199242.2 | |
WAS | ChrX:48547690 | c.1339-19_1339-11delTGATCCCTGinsATCTGCAGACC | NM_000377.2 | |
ZAP70 | Chr2:98349927 | c.838-80G>A | NM_001079.3 | rs113994173 |
ZAP70 | Chr2:98354447 | c.1624-11G>A | NM_001079.3 | rs730880318 |
Added and removed genes from the panel
Genes added | Genes removed |
---|---|
ALPI ARHGEF1 ATP6AP1 C17ORF62 CDK9 DBR1 DNASE2 EFL1 FCHO1 IL23R IL2RB IL6ST LIG1 POLD1 POMP PRG4 RELA RIPK1 SLC39A7 SPPL2A SRP54 TGFB1 TNFRSF9 TTC37 |
Test Strengths
- 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
- Our Nucleus online portal providing transparent and easy access to quality and performance data at the patient level
- Our publicly available analytic validation demonstrating complete details of test performance
- ~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: 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).
- 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).
- Low level mosaicism (variant with a minor allele fraction of 14.6% is detected with 90% probability)
- 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 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.
Performance of Blueprint Genetics high-quality, clinical grade NGS sequencing assay for panels.
Sensitivity % (TP/(TP+FN) | Specificity % | |
---|---|---|
Single nucleotide variants | 99.89% (99,153/99,266) | >99.9999% |
Insertions, deletions and indels by sequence analysis | ||
1-10 bps | 96.9% (7,563/7,806) | >99.9999% |
11-50 bps | 99.13% (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/duplication | 98.7% | 100.00% |
Microdeletion/-duplication sdrs (large CNVs, n=37)) | ||
Size range (0.1-47 Mb) | 100% (37/37) | |
The performance presented above reached by Blueprint Genetics high-quality, clinical grade NGS sequencing assay with the following coverage metrics | ||
Mean sequencing depth | 143X | |
Nucleotides with >20x sequencing coverage (%) | 99.86% |
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 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. 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 <20X sequencing depth if applicable. This reflects our mission to build fully transparent diagnostics where ordering providers can easily visualize the 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 is orthogonal confirmation. Sequence variants classified as pathogenic, likely pathogenic and variants of uncertain significance (VUS) are confirmed using bi-directional Sanger sequencing when they do not meet our stringent NGS quality metrics for a true positive call. Reported heterozygous and homo/hemizygous copy number variations with a size <10 and <3 target exons are confirmed by orthogonal methods such as qPCR if the specific CNV has been seen and confirmed 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, abstracts and variant databases used to help ordering providers 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. 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 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.
Other
- Autoinflammatory Alliance
- CAPS community
- Chronic Granulomatous Disease Association
- Chronic Granulomatous Disorder Society
- Dyskeratosis Congenita Outreach
- European Society for Immunodeficiencies
- Foundation for Children with Atypical HUS
- GeneReviews - *ELANE*-Related Neutropenia
- GeneReviews - *WAS*-Related Disorders
- GeneReviews - Chronic Granulomatous Disease
- GeneReviews - Dyskeratosis Congenita
- GeneReviews - Dyskeratosis Congenita
- GeneReviews - ELANE-Related Neutropenia
- GeneReviews - Familial Mediterranean Fever
- GeneReviews - Periodic Fever Syndrome
- GeneReviews - Severe Combined Immune Deficiency
- GeneReviews - Wiskott-Aldrich Syndrome
- GeneReviews - X-Linked Severe Combined Immunodeficiency
- Immune Deficiency Foundation
- Living with Chronic Granulomatous Disease
- NORD - Chronic Granulomatous Disease
- NORD - Cyclic Neutropenia
- NORD - DyskeratosisCongenita
- NORD - Dyskeratosis Congenita
- NORD - Familial Mediterranean Fever
- NORD - Muckle-Wells Syndrome
- NORD - Severe Chronic Neutropenia
- NORD - Severe Combined Immune Deficiency
- NORD - Wiskott-Aldrich Syndrome
- National Neutropenia Network
- Neutropenia Support Association
- Picard, C. et al. International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity. J Clin Immunol. 2018 Jan;38(1):96-128.
- Primary Immunodeficiency UK
- Wiskott-Aldrich Foundation