ClinVar Miner

Submissions for variant NM_000123.4(ERCC5):c.2383G>A (p.Ala795Thr)

gnomAD frequency: 0.00001  dbSNP: rs751772171
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001113896 SCV001271706 uncertain significance Xeroderma pigmentosum, group G 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx RCV001555508 SCV001776943 uncertain significance not provided 2021-06-23 criteria provided, single submitter clinical testing Reported the heterozygous state in two related individuals diagnosed with renal cell carcinoma; however, those individuals also harbored a pathogenic variant in the BAP1 gene (Popova 2013); Observed in one individual with xeroderma pigmentosum group G who was heterozygous for both the A795T variant and a frameshift variant in the ERCC5 gene (Fassihi 2016); Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23684012, 26884178, 27535533)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002469347 SCV002766594 uncertain significance not specified 2022-11-06 criteria provided, single submitter clinical testing Variant summary: ERCC5 c.2383G>A (p.Ala795Thr) results in a non-conservative amino acid change located in the XPG-I domain (IPR006086) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251334 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2383G>A has been reported in the literature in at least one individual affected with Xeroderma Pigmentosum (Fassihi_2016). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have assessed the variant since 2014: all three classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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