ClinVar Miner

Submissions for variant NM_002085.5(GPX4):c.502-1del

dbSNP: rs1555716575
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521481 SCV000620225 likely pathogenic not provided 2024-10-21 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24706940, 35718083)
Institute of Human Genetics, University of Leipzig Medical Center RCV001844185 SCV005368274 likely pathogenic Spondylometaphyseal dysplasia, Sedaghatian type 2024-06-17 criteria provided, single submitter clinical testing Criteria applied: PVS1_STR,PM2,PM3
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV001844185 SCV001870477 pathogenic Spondylometaphyseal dysplasia, Sedaghatian type 2021-04-29 no assertion criteria provided research
Royal Medical Services, Bahrain Defence Force Hospital RCV001844185 SCV005061399 uncertain significance Spondylometaphyseal dysplasia, Sedaghatian type no assertion criteria provided clinical testing The GPX4 variant c.523del p.(Val175Phefs*?) creates a shift in the reading frame starting at codon 175 with unknown location of the terminating stop codon. According to HGMD Professional 2020.3, loss of function is not known disease mechanism for this gene. To date, only one loss of function variant has been described. In gnomAD, the GPX4 gene seems to be tolerant for loss of function (pLI = 0). This variant has not yet been described in the literature in individuals with GPX4-related disorder. ClinVar lists this variant as uncertain (clinical testing, Variation ID: 451510). Thus, it is classified as variant of uncertain significance (class 3) according to the recommendations of CENTOGENE and ACMG.

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