PMC Inborn Errors of Immunity and Cytopenias Panel

Associated Conditions
- severe combined immunodeficiency
- combined immunodeficiency
- combined immunodeficiency with syndromic features
- major histocompatibility complex class I and II deficiencies
- dyskeratosis congenita
- agammaglobulinemia and hypogammaglobulinemia
- hyper IgM syndrome
- hyper IgE syndrome, including Netherton syndrome
- monogenic common variable immune deficiency
- chronic mucocutaneous candidiasis
- herpes simplex encephalitis
- epidermodysplasia verruciformis
- WHIM syndrome
- Mendelian susceptibility to mycobacterial infections
- autoimmune lymphoproliferative syndrome
- familial hemophagocytic lymphohistiocytosis and related disorders
- Hermansky-Pudlak syndrome
- congenital neutropenia
- chronic granulomatous disease
- leukocyte adhesion deficiency
- pulmonary alveolar proteinosis
- immunodeficiency- centromeric instability- facial anomalies syndrome
- complement deficiencies
- monogenic congenital diarrhea
- monogenic autoinflammatory syndromes
- monogenic autoimmunity
- periodic fever syndromes
- familial cold autoinflammatory syndromes
- familial Mediterranean fever
- monogenic inflammatory bowel disease
- activated PI3K-delta syndrome
- congenital dyserythropoietic anemia
- Majeed syndrome
- primary ciliary dyskinesia
- Cystic fibrosis
- atypical hemolytic uremic syndrome
- thrombotic thrombocytopenic purpura
- sitosterolemia
- congenital sideroblastic anemia
- familial essential thrombocythemia
- congenital amegakaryocytic thrombocytopenia
- Constitutional mismatch repair deficiency syndrome (CMMR-D)
- Coats Plus syndrome
- Pulmonary fibrosis
- Aplastic anemia, Myelodysplastic syndrome, Acute myelogenous leukemia, Bone marrow failure
- POT1 tumor predisposition
- Diamond-Blackfan anemia
- Fanconi anemia (FA)
- Glanzmann thrombasthenia
- Bernard-Soulier syndrome
- Wiskott-Aldrich syndrome
- Familial platelet disorder with associated myeloid malignancy

Methodology

Targeted Exome/ Slice Exome (Next Generation Sequencing including Copy Number Variation)

Coverage

120x

Ordering information

Turnaround Time: 10 business days

Preferred Speciment: Saliva Kits (available upon request)

Alternate Specimens: Nail clippings or 3-mL whole blood in purple top EDTA tube

Request a specimen collection kit

Limitations

All sequencing technologies have limitations. A negative result from this analysis does not rule out a possible genetic diagnosis as some variants may not be detected by this test. This test is not designed to detect low level mosaicism, structural rearrangements, indels >40bp, deep intronic variants of unknown clinical significance, or large cytogenetic CNVs. Certain inherent qualities of the human genome, for example repetitive regions/homopolymers, GC rich, pseudogenes, and rare polymorphisms, pose significant technical challenges such as sequence misalignment that may potentially impact the accuracy of the results. False negative results may also occur in the setting of allogeneic bone marrow, stem cell transplantation, active or chronic hematologic conditions, recent blood transfusions, suboptimal DNA quality or PCR trace contamination. Other potential sources of error include sample mix-ups and clerical issues.

References
- 1. Richards S et al. Genetics in medicine. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. 2015 May;17(5):405-24 (PMID: 25741868)
- 2. GnomAD (gnomAD)
- 3. CSPEC (ClinGen variant classification rules registry) Criteria Specification Registry
- 4. Normal copy number variation in healthy individuals database of genomic variants: http://dgv.tcag.ca/dgv/app/home
- 5. Riggs, E.R., Andersen, E.F., Cherry, A.M. et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med 22, 245–257 (2020). https://doi.org/10.1038/s41436-019-0686-8
- 6. Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, Maglott DR. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 2014 Jan 1;42(1):D980-5. doi: 10.1093/nar/gkt1113. PubMed PMID: 24234437.
- 7. Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), Copyright® 1966-2012. World Wide Web URL: http://omim.org.
- 8. http://tinyurl.com/ACMGv4 (ACMG/ Clingen draft Interpretation SOP); clingen_variant-curation_sopv1.pdf

Tagged Genes

Primary panel:

574 genes selected

ABCB7 ABCG5 ABCG8 ACAN ACD ACP5 ACTB ACTN1 ADA ADA2 ADAM17 ADAMTS13 ADAR ADGRE2 AICDA AIRE AK2 AK7 ALAS2 ALG6 ALPK1 ANGPT1 ANKRD26 ANKZF1 ANO6 AP3B1 AP3D1 ARHGEF1 ARMC4 ARPC1B ASAH1 ATM ATP6AP1 ATR B2M BACH2 BCL10 BCL11B BLM BLNK BLOC1S3 BLOC1S6 BRCA1 BRCA2 BRIP1 BTK C11orf70 C15orf41 C17orf62 C1QA C1QB C1QC C1S C2 C3 C5 C6 C7 C8A C8B C9 CARD11 CARD14 CARD8 CARD9 CARMIL2 CASP10 CASP8 CBL CCBE1 CCDC103 CCDC114 CCDC151 CCDC39 CCDC40 CCDC65 CCNO CD19 CD247 CD27 CD3D CD3E CD3G CD40 CD40LG CD46 CD55 CD59 CD79A CD79B CD81 CD8A CDAN1 CDC42 CDCA7 CEBPE CEP164 CFAP298 CFB CFD CFH CFI CFP CFTR CHD7 CHEK2 CIB1 CIITA CLCN7 CLPB COL7A1 COPA CORO1A CR2 CSF2RA CSF2RB CSF3R CTC1 CTLA4 CTPS1 CTSC CXCR2 CXCR4 CYBA CYBB CYCS CYP27A1 DBR1 DCLRE1C DDX41 DDX58 DEF6 DGAT1 DGKE DIAPH1 DKC1 DNAAF1 DNAAF2 DNAAF3 DNAAF4 DNAAF5 DNAH1 DNAH11 DNAH5 DNAH8 DNAH9 DNAI1 DNAI2 DNAJB13 DNAJC21 DNAL1 DNASE1L3 DNASE2 DNMT3B DOCK2 DOCK8 DRC1 DSG1 DTNBP1 DUOX2 EFL1 EIF2AK3 ELANE EPCAM EPG5 ERBIN ERCC2 ERCC3 ERCC4 ERCC6L2 ETV6 EXTL3 FADD FANCA FANCB FANCC FANCD2 FANCE FANCF FANCG FANCI FANCL FANCM FAS FASLG FAT4 FCHO1 FERMT1 FERMT3 FLI1 FNIP1 FOXI3 FOXN1 FOXP3 FPR1 G6PC G6PC3 G6PD GAS8 GATA1 GATA2 GFI1 GINS1 GLRX5 GP1BA GP6 GP9 GTF2E2 GTF2H5 GUCY2C HAX1 HELLS HMOX1 HPS1 HPS3 HPS4 HPS5 HPS6 HTRA2 HYOU1 ICOS ICOSLG IFIH1 IFNAR1 IFNAR2 IFNGR1 IFNGR2 IGLL1 IKBKB IKZF1 IL10 IL10RA IL10RB IL12B IL12RB1 IL12RB2 IL17F IL17RA IL17RC IL18BP IL1RN IL21 IL21R IL23R IL2RA IL2RB IL2RG IL36RN IL6R IL6ST IL7R IRAK4 IRF2BP2 IRF4 IRF7 IRF8 IRF9 ISG15 ITCH ITGA2B ITGAM ITGB2 ITGB3 ITK JAGN1 JAK1 JAK2 JAK3 KAT6A KDM1A KDM6A KIF23 KIT KLF1 KLHDC8B KMT2A KMT2D LAMTOR2 LARS2 LAT LCK LCT LIG1 LIG4 LIPA LPIN2 LRBA LRRC56 LRRC6 LRRC8A LYN LYST MAD2L2 MAGT1 MALT1 MAP3K14 MBD4 MCIDAS MCM4 MECOM MEFV MKL1 MLH1 MOGS MPL MPLKIP MS4A1 MSH2 MSH6 MSN MTHFD1 MVK MYD88 MYH9 MYO5B MYSM1 NAF1 NBAS NBN NCF2 NCF4 NCKAP1L NCSTN NDUFB11 NEUROG3 NF1 NFAT5 NFE2L2 NFKB1 NFKB2 NFKBIA NHEJ1 NHP2 NLRC4 NLRP1 NLRP12 NLRP3 NME8 NOD2 NOP10 NOTCH2 NPAT NSMCE3 OAS1 OFD1 ORAI1 OSTM1 OTULIN P2RY12 PALB2 PARN PAX1 PEPD PGM3 PIH1D3 PIK3CD PIK3R1 PLA2G4A PLCG2 PLG PLVAP PMM2 PMS2 PNLIP PNP POLA1 POLD1 POLD2 POLE POLE2 POLR3A POLR3F POMP POT1 PRF1 PRKCD PRKDC PSENEN PSMA3 PSMB4 PSMB8 PSMG2 PSTPIP1 PTEN PTPRC PUS1 RAB27A RAC2 RAD51 RAD51C RAG1 RAG2 RANBP2 RASGRP1 RASGRP2 RBCK1 RBM8A RECQL4 REL RELA RELB RFWD3 RFX5 RFXANK RFXAP RHOH RIPK1 RMRP RNASEH2A RNASEH2B RNASEH2C RNF113A RNF168 RNF31 RNU4ATAC RORC RPGR RPL11 RPL15 RPL18 RPL19 RPL23 RPL26 RPL27 RPL31 RPL35 RPL35A RPL5 RPL9 RPS10 RPS15A RPS19 RPS24 RPS26 RPS27 RPS28 RPS29 RPS7 RPSA RSPH1 RSPH3 RSPH4A RSPH9 RTEL1 RUNX1 SAMD9 SAMD9L SAMHD1 SAR1B SBF2 SCO2 SEC23B SEC61A1 SEMA3E SERPING1 SGPL1 SH2D1A SH3BP2 SH3KBP1 SI SIAE SKIV2L SLC10A2 SLC19A2 SLC25A38 SLC26A3 SLC29A3 SLC35C1 SLC37A4 SLC39A7 SLC46A1 SLC51B SLC5A1 SLC7A7 SLC9A3 SLX4 SMARCAL1 SMARCD2 SNX10 SP110 SPAG1 SPINK5 SPINT2 SPPL2A SRP54 SRP72 STAT1 STAT2 STAT3 STAT4 STAT5B STIM1 STK4 STN1 STX11 STX3 STXBP2 TAOK2 TAP1 TAP2 TAPBP TAZ TBX1 TBXA2R TCF3 TCIRG1 TCN2 TERC TERF2IP TERT TET2 TFRC TGFB1 TGFBR1 TGFBR2 THBD THPO TICAM1 TIMM50 TINF2 TLR3 TLR7 TMC6 TMC8 TMEM173 TMPRSS15 TNFAIP3 TNFRSF11A TNFRSF13B TNFRSF13C TNFRSF1A TNFRSF4 TNFRSF6B TNFRSF9 TNFSF11 TNFSF12 TONSL TOP2B TP53 TP63 TPP2 TRAF3 TRAF3IP2 TREX1 TRNT1 TSR2 TTC37 TTC7A TUBB1 TYK2 UBE2T UNC13D UNC45A UNC93B1 UNG USB1 VAV1 VIPAS39 VPS13B VPS33B VPS45 WAS WDR1 WIPF1 WNT2B WRAP53 XIAP XRCC2 YARS2 ZAP70 ZBTB24 ZCCHC8 ZMYND10 ZNF341

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Test Description

Associated Conditions

Methodology

Coverage

Ordering information

Limitations

References

Tagged Genes