ClinVar Miner

Submissions for variant NM_000082.4(ERCC8):c.479C>T (p.Ala160Val)

gnomAD frequency: 0.00001  dbSNP: rs121434325
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000059647 SCV000521089 likely pathogenic not provided 2021-03-26 criteria provided, single submitter clinical testing Identified in the presence of a second ERCC8 variant, phase unknown, in a patient with Cockayne syndrome (Ridley et al., 2005).; Published studies demonstrate a damaging effect; specifically, this variant causes the deletion of exon 5 in the transcipt (Nardo et al., 2009); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 29742419, 19329487, 15744458, 29572252, 33199595)
Labcorp Genetics (formerly Invitae), Labcorp RCV000059647 SCV001575796 pathogenic not provided 2023-12-02 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 160 of the ERCC8 protein (p.Ala160Val). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs121434325, gnomAD 0.002%). This missense change has been observed in individual(s) with Cockayne syndrome type A (PMID: 15744458, 29572252). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1717). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Studies have shown that this missense change results in deletion of exon 5 and introduces a premature termination codon (PMID: 15744458). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic RCV000059647 SCV002520026 likely pathogenic not provided 2022-01-12 criteria provided, single submitter clinical testing PP3, PP4, PM2, PM3, PM5, PS4_moderate
OMIM RCV000001787 SCV000021943 pathogenic Cockayne syndrome type 1 2005-01-01 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000059647 SCV000091217 not provided not provided no assertion provided not provided
Counsyl RCV000001787 SCV000800611 uncertain significance Cockayne syndrome type 1 2017-10-25 flagged submission clinical testing

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