Primary Immunodeficiency Panel

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

Test code: IM0301

The Blueprint Genetics Primary Immunodeficiency Panel is a 230 gene test for genetic diagnostics of patients with clinical suspicion of autoinflammatory disorders, combined immunodeficiencies, complement deficiencies, congenital defects of phagocytes, defects in innate immunity, diseases of immune dysregulation or immunodeficiencies with antibody defects.

Primary immunodeficiencies (PIDs) are a very heterogenous group of diseases. This Panel covers comprehensively genes associated with PIDs inherited either in autosomal recessive, autosomal dominant or X-linked manner. In addition to familial diseases, some specific types of PIDs are often caused by de novo mutations. This comprehensive Panel includes Complement System Disorder Panel, Severe Combined Immunodeficiency Panel, Dyskeratosis Congenita Panel, Autoinflammatory Syndrome Panel, Congenital Neutropenia Panel and Chronic Granulomatous Disease Panel and has differential diagnostics power to any phenotypes detectable by these Panels.

About Primary Immunodeficiency

Primary immunodeficiencies (PIDs) are a genetically very heterogenous group of diseases. The International Union of Immunological Societies Expert Committee categorize PIDs into nine different catogories: 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 innate immunity, 7) autoinflammatory disorders, 8) complement deficiencies and 9) phenocopies of PIDs. Despite of a heterogenous genetic basis, the core symptoms are often very similar complicating the definite diagnosis and many PIDs may be included in more than one category. Treatment choice without specific information on the causative gene and mutation 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 nonimmune manifestations. The prevalence of individual PIDs have a wide range, but combined prevalence of all primary immunodeficiencies is reported to be as high as 5-8:10 000. Some recently found PIDs are extremely rare.

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 Primary Immunodeficiency Panel and their clinical significance
Gene Associated phenotypes Inheritance ClinVar HGMD
ACP5 Spondyloenchondrodysplasia with immune dysregulation AR 10 26
ACTB* Baraitser-Winter syndrome AD 38 27
ADA Severe combined immunodeficiency due to adenosine deaminase deficiency AR 38 87
ADAR Dyschromatosis symmetrica hereditaria, Aicardi-Goutières syndrome AD/AR 21 205
ADIPOQ Complement system AD/AR 2 8
ADIPOR1* Complement system AD/AR 4
ADIPOR2 Complement system AD/AR
AICDA Immunodeficiency with hyper-IgM AD/AR 14 50
AIRE Autoimmune polyendocrinopathy syndrome AD/AR 49 125
AK2 Reticular dysgenesis AR 14 17
AP3B1 Hermansky-Pudlak syndrome AR 14 25
ARMC4* Ciliary dyskinesia AR 13 15
ATM Breast cancer, Ataxia-Telangiectasia AD/AR 646 923
BLM Bloom syndrome AR 83 91
BTK Hypogammaglobulinemia, Agammaglobulinemia and isolated hormone deficiency, Agammaglobulinemia XL 91 898
C1QA C1q deficiency AR 2 7
C1QB C1q deficiency AR 4 7
C1QBP Primary immunodeficiency AD/AR 6
C1QC C1q deficiency AR 4 7
C1R Immunodeficiency AD/AR 14 16
C1S Complement component C1s deficiency AR 4 8
C2* Complement component 2 deficiency AR 4 6
C3 Hemolytic uremic syndrome, atypical, Complement component 3 deficiency AD/AR 5 82
C3AR1 Complement system AD/AR 1 3
C4A* Blood group, Chido/Rodgers system BG 1 5
C4B* Complement component 4B deficiency AR 8
C4BPA Complement system AD/AR 2
C4BPB Complement system AD/AR
C5 Eculizumab, poor response to, Complement component 5 deficiency AD/AR 5 17
C5AR1 Complement system AD/AR
C5AR2 Complement system AD/AR 2
C6 Complement component 6 deficiency AR 7 11
C7 Complement component 7 deficiency AR 14 29
C8A Complement component 8 deficiency AR 2 5
C8B Complement component 8 deficiency AR 7 7
C8G Immunodeficiency AD/AR
C9 Complement component 9 deficiency AR 7 7
CARD11 B-cell expansion with NFKB and T-cell anergy, Immunodeficiency AD/AR 10 8
CARD14 Psoriasis AD 9 25
CASP8 Caspase 8 defiency AR 2 3
CASP10 Autoimmune lymphoproliferative syndrome AD 5 6
CCDC39 Ciliary dyskinesia AR 16 38
CCDC40 Ciliary dyskinesia AR 19 32
CCDC65 Ciliary dyskinesia AR 1
CCDC103 Ciliary dyskinesia AR 3 4
CCDC114 Ciliary dyskinesia AR 6 7
CCNO Ciliary dyskinesia AR 9 9
CD3D Immunodeficiency AR 3 5
CD3E Immunodeficiency AR 3 7
CD3G Immunodeficiency AR 3 3
CD8A CD8 deficiency AR 1 1
CD19 Immunodeficiency, common variable AR 8 8
CD27 Lymphoproliferative syndrome AR 2 8
CD40 Immunodeficiency with Hyper-IgM AR 5 9
CD40LG Immunodeficiency, with hyper-IgM XL 27 227
CD46* Hemolytic uremic syndrome, atypical AD/AR 4 64
CD55 Blood group, Cromer system BG 7 6
CD59 CD59 deficiency AR 3 6
CD93 Complement system AD/AR
CD247 Immunodeficiency AR 7 4
CECR1 Polyarteritis nodosa, ADA2 deficiency AR 15 41
CFB Complement factor B deficiency, Hemolytic uremic syndrome, atypical AD/AR 2 21
CFD Complement factor D deficiency AR 2 3
CFH* Hemolytic uremic syndrome, atypical, Complement factor H deficiency AD/AR 17 259
CFI Hemolytic uremic syndrome, atypical, Complement factor I deficiency AD/AR 7 123
CFP Properdin deficiency XL 5 17
CIITA Bare lymphocyte syndrome AR 7 14
CLU Complement system AD/AR 16
COLEC11 3MC syndrome AR 6 10
CORO1A* Immunodeficiency AR 38 6
CR1* Blood group, Knops system BG 1 15
CR2 Common variable immunodeficiency AR 2 5
CRP Complement system AD/AR
CSF2RA* Surfactant metabolism dysfunction, pulmonary XL 2 17
CTC1 Cerebroretinal microangiopathy with calcifications and cysts AR 15 29
CTLA4 AD 8 22
CTSC Periodontitis, juvenile, Haim-Munk syndrome, Papillon-Lefevre syndrome AR 16 91
CYBA Chronic granulomatous disease AR 12 66
CYBB Chronic granulomatous disease, Immunodeficiency XL 58 749
DCLRE1C* Omenn syndrome, Severe combined immunodeficiency with sensitivity to ionizing radiation AR 16 83
DDX58 Singleton-Merten syndrome AD 4 2
DGKE Nephrotic syndrome AR 13 27
DKC1 Hoyeraal-Hreidarsson syndrome, Dyskeratosis congenita XL 47 71
DNAAF1 Ciliary dyskinesia AR 9 30
DNAAF2 Ciliary dyskinesia AR 6 3
DNAAF3 Primary ciliary dyskinesia AD/AR 6 3
DNAAF5 Ciliary dyskinesia AR 2 2
DNAH5 Ciliary dyskinesia AR 60 141
DNAH11* Ciliary dyskinesia AR 30 90
DNAI1 Ciliary dyskinesia AR 12 28
DNAI2 Ciliary dyskinesia AR 11 6
DNAL1 Ciliary dyskinesia AR 3 1
DNMT3B Immunodeficiency-centromeric instability-facial anomalies syndrome AR 15 44
DOCK2 Immunodeficiency AR 5 6
DOCK8 Hyper-IgE recurrent infection syndrome AR 34 151
DRC1 Primary ciliary dyskinesia AD/AR 3 2
DYX1C1 Ciliary dyskinesia AR 9 11
ELANE Neutropenia AD 37 213
FAS Autoimmune lymphoproliferative syndrome AD/AR 24 129
FCN1 Complement system AD/AR 3
FCN2 Complement system AD/AR
FCN3 Immunodeficiency due to Ficolin 3 deficiency AR 1
FERMT3 Leukocyte adhesion deficiency AR 8 14
FOXP3 Immunodysregulation, polyendocrinopathy, and enteropathy XL 24 80
G6PC3 Neutropenia, severe congenital, Dursun syndrome AR 12 37
G6PD Glucose-6-phosphate dehydrogenase deficiency XL 39 221
GATA2 Myelodysplastic syndrome, Chronic neutropenia associated with monocytopenia, evolving to myelodysplasia and acute myeloid leukemia, Acute myeloid leukemia, Emberger syndrome, Immunodeficiency AD 22 105
HAX1 Neutropenia, severe congenital AR 9 19
HYDIN* Primary ciliary dyskinesia AD/AR 5 15
IFIH1 Singleton-Merten syndrome AD 13 15
IFNGR1 Immunodeficiency AD/AR 15 39
IFNGR2 Immunodeficiency AR 4 17
IGHM Agammaglobulinemia AR 6 15
IGLL1* Agammaglobulinemia AR 3 2
IKBKG* Incontinentia pigmenti, Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency, Immunodeficiency, Invasive pneumococcal disease, recurrent, isolated, Osteopetrosis with ectodermal dysplasia and immune defect (OLEDAID) XL 43 143
IL1RN Osteomyelitis, sterile multifocal, with periostitis and pustulosis AR 6 13
IL2RA Interleukin 2 receptor, alpha, deficiency AR 5 6
IL2RG Combined immunodeficiency XL 39 220
IL7* Interleukin 7 deficiency, Generalized verrucosis, HPV susceptibility AD/AR
IL7R Severe combined immunodeficiency, , T-cell negative, B-cell positive, NK cell positive AR 19 47
IL10RA Inflammatory bowel disease AR 5 36
IL10RB Inflammatory bowel disease AR 2 15
IL12RB1 Immunodeficiency AR 9 81
IL36RN Pustular psoriasis, generalized AR 6 23
ISG15 Immunodeficiency, with basal ganglia calcification AR 3 3
ITGB2 Leukocyte adhesion deficiency AR 33 114
ITK Lymphoproliferative syndrome AR 3 10
JAGN1 Neutropenia, severe congenital AR 8 8
JAK3 Severe combined immunodeficiency, , T cell-negative, B cell-positive, natural killer cell-negative AR 27 63
LCK Immunodeficiency AR 2 3
LIG4 Severe combined immunodeficiency with sensitivity to ionizing radiation, LIG4 syndrome AR 14 35
LPIN2 Majeed syndrome AR 7 10
LRBA Common variable immunodeficiency AR 14 58
LRRC6 Ciliary dyskinesia AR 7 16
LYST Chediak-Higashi syndrome AR 46 87
MAGT1 Immunodeficiency, with magnesium defect, Epstein-Barr virus infection and neoplasia XL 5 14
MALT1 Immunodeficiency AR 3 5
MASP1 3MC syndrome AR 7 17
MASP2 MASP2 deficiency AR 2
MAT2A* Complement system AD/AR 2
MEFV Familial Mediterranean fever AD/AR 25 176
MRE11A Ataxia-telangiectasia-like disorder-1 AR 35 43
MVK Mevalonic aciduria, Hyper-IgD syndrome AR 29 173
NBN Breast cancer, Nijmegen breakage syndrome AD/AR 95 65
NCF1* Chronic granulomatous disease AR 18 37
NCF2 Chronic granulomatous disease AR 13 62
NCF4 Granulomatous disease AR 4 2
NFKB1 Common variable immunodeficiency AD 4 10
NFKB2 Common variable immunodeficiency AD 6 9
NFKBIA Ectodermal dysplasia, anhidrotic, with T-cell immunodeficiency AD 4 10
NHEJ1 Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation AR 14 15
NHP2 Dyskeratosis congenita AR 3 3
NLRP3 Neonatal onset multisystem inflammatory disease (NOMID), Muckle-Wells syndrome, Chronic infantile neurologic cutaneous articular (CINCA) syndrome AD 19 127
NLRP12 Familial cold autoinflammatory syndrome AD 3 10
NME8 Ciliary dyskinesia AR 1 5
NOD2 Blau syndrome, Sarcoidosis, early-onset AD/AR 12 60
NOP10 Dyskeratosis congenita AR 1 1
NRAS Noonan syndrome AD 31 14
OFD1 Simpson-Golabi-Behmel syndrome, Retinitis pigmentosa, Orofaciodigital syndrome, Joubert syndrome XL 133 156
ORAI1 Immunodeficiency AR 8 12
PIGA* Multiple congenital anomalies-hypotonia-seizures syndrome XL 23 17
PIK3CD* Immunodeficiency AD 5 11
PIK3R1 Agammaglobulinemia AD/AR 27 19
PLCG2 Familial cold autoinflammatory syndrome 3 (PLAID), Autoinflammation, antibody deficiency, and immune dysregulation syndrome (APLAID) AD 7 9
PMS2* Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposis AD/AR 196 284
PNP Purine nucleoside phosphorylase deficiency AR 10 33
PRF1 Lymphoma, non-Hodgkin, Aplastic anemia, adult-onset, Hemophagocytic lymphohistiocytosis AR 17 169
PRKDC Immunodeficiency AR 6 7
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 4 9
PSTPIP1 Pyogenic sterile arthritis, pyoderma gangrenosum, and acne AD 5 27
PTPRC Severe combined immunodeficiency, , T-cell negative, B-cell positive, NK cell positive AR 4 5
PTX3 Complement system AD/AR
RAB27A Griscelli syndrome, Elejalde syndrome AR 14 49
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 43 181
RAG2 Omenn syndrome, Combined cellular and humoral immune defects with granulomas AR 22 78
RFX5 Bare lymphocyte syndrome AR 5 6
RFXANK MHC class II deficiency AR 6 14
RFXAP Bare lymphocyte syndrome AR 5 7
RHOH T-cell immunodeficiency with epidermodysplasia verruciformis AD/AR 1
RMRP Cartilage-hair hypoplasia, Metaphyseal dysplasia without hypotrichosis, Anauxetic dysplasia AR 29 123
RNASEH2A Aicardi-Goutières syndrome AR 13 21
RNASEH2B Aicardi-Goutières syndrome AR 10 40
RNASEH2C Aicardi-Goutières syndrome AR 6 14
RPGR Retinitis pigmentosa XL 62 202
RSPH1 Ciliary dyskinesia AR 11 10
RSPH4A Ciliary dyskinesia AR 8 21
RSPH9 Ciliary dyskinesia AR 4 11
RTEL1 Pulmonary fibrosis and/or bone marrow failure, Dyskeratosis congenita AD/AR 32 44
SAMHD1 Aicardi-Goutières syndrome AR 22 51
SBDS* Aplastic anemia, Shwachman-Diamond syndrome, Severe spondylometaphyseal dysplasia AD/AR 18 88
SERPING1 Angioedema AD/AR 26 535
SH2D1A Lymphoproliferative syndrome XL 14 125
SLC37A4 Glycogen storage disease AR 27 108
SMARCAL1 Schimke immunoosseous dysplasia AR 12 75
SP110 Hepatic venoocclusive disease with immunodeficiency AR 7 7
SPAG1 Primary ciliary dyskinesia AD/AR 13 10
SPINK5 Netherton syndrome AR 18 82
STAT1 Immunodeficiency AD/AR 31 116
STAT2 Immunodeficiency AR 2 6
STAT3 Hyper-IgE recurrent infection syndrome, Autoimmune disease, multisystem, infantile onset AD 43 145
STAT4 Behçet disease, Juvenile rheumatoid factor-negative polyarthritis, Oligoarticular juvenile arthritis, Pediatric systemic lupus erythematosus AD/AR
STAT5B* Growth hormone insensitivity with immunodeficiency AR 5 10
STIM1 Stormorken syndrome, Immunodeficiency AD/AR 12 20
STK4 T-cell immunodeficiency syndrome, recurrent infections, autoimmunity, AR 3 7
STXBP2 Hemophagocytic lymphohistiocytosis, familial AR 8 62
TAP1 Bare lymphocyte syndrome AR 2 7
TAP2 Bare lymphocyte syndrome AR 2 8
TAPBP Bare lymphocyte syndrome AR 1 2
TBX1 Conotruncal anomaly face syndrome AD 11 62
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
TMEM173 STING-associated vasculopathy, infantile-onsent (SAVI) AD 3 7
TNFRSF1A Periodic fever (TNF receptor-associated periodic syndrome) AD 19 99
TNFRSF4 Immunodeficiency AR 1
TNFRSF13B Common variable immunodeficiency, Immunoglobulin A deficiency AD/AR 6 47
TRAC T-cell receptor-alpha/beta deficiency AR 1 1
TREX1 Vasculopathy, retinal, with cerebral leukodystrophy, Chilblain lupus, Aicardi-Goutières syndrome AD/AR 27 66
TYK2 Immunodeficiency AR 7 8
UNC119 Immunodeficiency AR 1 5
USB1 Poikiloderma with neutropenia AR 4 22
VSIG4 Complement system XL 1
VTN Complement system AD/AR
WAS Neutropenia, severe congenital, Thrombocytopenia, Wiskott-Aldrich syndrome XL 44 431
WRAP53 Dyskeratosis congenita AR 7 5
XIAP* Lymphoproliferative syndrome XL 4 83
ZAP70 Selective T-cell defect AR 13 26
ZMYND10 Ciliary dyskinesia AR 6 16

*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
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
DKC1 ChrX:153991099 c.-142C>G NM_001363.3 rs199422241
DOCK8 Chr9:368196 c.1797+61A>C NM_203447.3 rs786205596
DOCK8 Chr9:271626 c.54-1G>T NM_203447.3 rs192864327
OFD1 ChrX:13773245 c.1130-22_1130-19delAATT NM_003611.2 rs312262865
OFD1 ChrX:13768358 c.935+706A>G NM_003611.2 rs730880283
PRKDC Chr8:48844056 c.1777-710dupA NM_006904.6 rs760771518
THBD Chr20:23030292 c.-151G>T NM_000361.2 rs16984852
ZAP70 Chr2:98349927 c.838-80G>A NM_001079.3 rs113994173

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 Primary Immunodeficiency Panel that covers classical genes associated with autoinflammatory disorders, combined immunodeficiencies, complement deficiencies, congenital defects of phagocytes, defects in innate immunity, diseases of immune dysregulation and immunodeficiencies with antibody defects. 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


ICD codes

Commonly used ICD-10 codes when ordering the Primary Immunodeficiency Panel

ICD-10 Disease
D80.9 Immunodeficiencies with antibody defects
D84.1 Complement deficiencies
D81.9 Combined immunodeficiencies

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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