PMC Inherited Platelet Disorders Including Thrombocytopenia Panel (new)

Associated Conditions
- Thrombotic thrombocytopenic purpura
- Glanzmann thrombasthenia
- Bernard-Soulier syndrome
- Hermansky-Pudlak syndrome
- Congenital amegakaryocytic thrombocytopenia
- Wiskott-Aldrich syndrome
- Leukocyte adhesion deficiency type 3
- Familial platelet disorder with associated myeloid malignancy

Methodology

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

Coverage

120x

Assay Information
- RBM8A: Analysis includes the non-coding variants NM_005105.4:c.-21G >A and c.67+32G >C.
- GP1BA: c.104delA (p.Lys35Argfs*4)| c.165_168delTGAG (p.Ser55Argfs*12)| c.376A >G (p.Asn126Asp)| c.434T >C (p.Leu145Pro)| c.515C >T (p.Ala172Val)| c.584_586delTCC (p.Leu195del)| c.673T >A (p.Cys225Ser)| c.1454dupT (p.Ser486Ilefs*12)| c.1480delA (p.Thr494Profs*59)| c.1601_1602delAT (p.Tyr534Cysfs*82)| c.1620G >A (p.Trp540*) variants only.
- EFL1: Deletion/duplication and sequencing analysis is not offered for exons 7| 15.
- ANKRD26: Sequencing analysis for exons 19 includes only cds +/- 0 bp.
- ANO6: Sequencing analysis for exons 10 includes only cds +/- 0 bp.

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:

297 genes selected

ABCA1 ABCC6 ABCG5 ABCG8 ACP5 ACSF3 ACTB ACTN1 ACVRL1 ADA2 ADAMTS13 ADAR AGK ANK1 ANKRD11 ANKRD26 ANO6 AP3B1 AP3D1 APC APOE AR ARID2 ARPC1B ARSA ATRN BAAT BLOC1S3 BLOC1S6 BRCA1 BRCA2 BRIP1 C1GALT1C1 C3 C3AR1 CBL CD19 CD209 CD36 CD40LG CD46 CD81 CDC42 CEP290 CFB CFH CFHR1 CFHR2 CFHR3 CFHR4 CFHR5 CFI CHEK2 CIITA CLCN7 COG7 COL1A2 COL4A4 COL4A5 COL5A1 COL5A2 CSMD1 CTC1 CTLA4 CYCS DCLRE1B DCLRE1C DGKE DIAPH1 DKC1 DMD DNAJC21 DOCK8 DTNBP1 EFL1 ELANE ELP1 ERCC4 ERCC6L2 ETV6 F10 F11 F13A1 F2 F5 F7 F8 FAH FANCA FANCB FANCC FANCD2 FANCE FANCF FANCG FANCI FANCL FANCM FAS FASN FBN2 FCN2 FERMT3 FGA FGB FGG FLI1 FLNA FOXP3 FYB FYB1 G6PC3 GALE GATA1 GATA2 GBA GBA1 GFI1B GGCX GJB2 GNE GP1BA GP1BB GP6 GP9 GPHN HOXA11 HPS1 HPS3 HPS4 HPS5 HPS6 HRG HSD17B4 IDS IFIH1 IGHMBP2 IKBKG IKZF1 IKZF5 ITGA2 ITGA2B ITGB2 ITGB3 ITK JAG1 KANSL1 KAT6A KCNV2 KDM5C KIF15 KLKB1 KMT2A KMT2B KMT2D LAMA2 LAMB2 LIG4 LIPA LOC100506422 LPA LPL LRBA LRP2 LYST MAD2L2 MAGEL2 MAGT1 MAN2B2 MAP2K2 MASTL MCEE MCFD2 MECOM MECP2 MMAA MMAB MMACHC MMADHC MMUT MPEG1 MPIG6B MPL MSH6 MTHFR MYH9 NBEAL2 NF1 NFKB1 NLRC4 NLRP3 NOD2 NPHP4 NPHS1 NPM1 NSD1 NSD2 P2RY12 PAH PALB2 PARN PEPD PIEZO1 PLA2G4A PLA2R1 PLAT PLCG1 PLG PMM2 PNKP POMP PQBP1 PRF1 PRKACG PROP1 PROS1 PSAP PTPN11 PTPRJ RAD51 RAD51C RASGRP2 RBM8A RFWD3 RHOG RNASEH2A RNASEH2B RNASEH2C RPL5 RPS19 RRAS RUNX1 SAG SALL4 SAMD9 SAMD9L SAMHD1 SBDS SERPINC1 SET SLC2A1 SLC2A2 SLC45A2 SLC46A1 SLC6A5 SLC7A7 SLFN14 SLX4 SMAD4 SMARCAL1 SMC1A SMPD1 SOCS1 SOS1 SPOP SPTB SRC SRP54 STAMBP STAT1 STAT3 STIM1 STN1 STT3B STXBP2 TBXA2R TBXAS1 TCF3 TCN2 TERT THBD THPO TLR7 TMEM67 TNFAIP3 TPM4 TPP2 TREX1 TRPC6 TSPEAR TUBB1 UBE2T UNC80 VIPAS39 VPS33B VWF WAS WDR1 WIPF1 WNT1 WRN WT1 XDH XRCC2 YARS2 ZNF469 ZNFX1

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Test Description

Associated Conditions

Methodology

Coverage

Assay Information

Ordering information

Limitations

References

Tagged Genes