ClinVar Miner

Submissions for variant NM_001083116.3(PRF1):c.82C>T (p.Arg28Cys)

gnomAD frequency: 0.00043  dbSNP: rs141660796
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000734558 SCV000862710 uncertain significance not provided 2018-08-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001085710 SCV001023963 benign Familial hemophagocytic lymphohistiocytosis 2 2025-01-13 criteria provided, single submitter clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000734558 SCV002009736 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002261199 SCV002542799 uncertain significance Autoinflammatory syndrome 2020-05-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002271577 SCV002556242 uncertain significance not specified 2022-06-29 criteria provided, single submitter clinical testing Variant summary: PRF1 c.82C>T (p.Arg28Cys) results in a non-conservative amino acid change located in the Membrane attack complex component/perforin (MACPF) domain (IPR020864) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0011 in 242388 control chromosomes (gnomAD), predominantly at a frequency of 0.0053 within the South Asian subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in PRF1 causing Familial Hemophagocytic Lymphohistiocytosis (0.0027), suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. c.82C>T has been reported in the literature in individuals affected with Hemophagocytic Lymphohistiocytosis (McCreary_2019, Shabrish_2021, Taieb_2021), Immune Thrombocytopenia (Boggio_2017) and Juvenile onset arthritis (Vastert_2010). These data indicate that the variant may be associated with disease. Three ClinVar submitters have assessed the variant since 2014: two classified the variant as VUS, and one as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Revvity Omics, Revvity RCV000734558 SCV003809851 uncertain significance not provided 2022-05-10 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000734558 SCV005411045 uncertain significance not provided 2024-05-14 criteria provided, single submitter clinical testing BS1

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