ClinVar Miner

Submissions for variant NM_000123.4(ERCC5):c.2620G>A (p.Ala874Thr) (rs121434576)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000018045 SCV000382117 uncertain significance Xeroderma pigmentosum, group G 2017-04-27 criteria provided, single submitter clinical testing The ERCC5 c.2620G>A (p.Ala874Thr) missense variant has been reported in a single study in which it was found in a compound heterozygous state with a stop-gained variant in one patient with a mild phenotype belonging to the xeroderma pigmentosum (XP) complementation group G (Emmert et al. 2002). The p.Ala874Thr variant was absent from 104 controls (Emmert et al. 2002) and is reported at a frequency of 0.00002 in the total population of the Exome Aggregation Consortium. Functional studies of the variant in patient fibroblasts showed a marked reduction in post-UV cell survival and DNA repair compared to wild type cells but nearly normal levels of mRNA expression. The variant protein was also shown to have residual ability to complement XP group G cells, consistent with the mild phenotype (Emmert et al. 2002). The p.Ala874Thr variant is located in the highly conserved I-region that is thought to be part of the active site of the enzyme. Based on the evidence, the p.Ala874Thr variant is considered to be of unknown significance but suspicious for pathogenicity for xeroderma pigmentosum. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000018045 SCV000038324 pathogenic Xeroderma pigmentosum, group G 2002-06-01 no assertion criteria provided literature only

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