ClinVar Miner

Submissions for variant NM_000082.4(ERCC8):c.613G>C (p.Ala205Pro)

gnomAD frequency: 0.00006  dbSNP: rs121434326
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000059650 SCV001588880 pathogenic not provided 2025-01-07 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 205 of the ERCC8 protein (p.Ala205Pro). This variant is present in population databases (rs121434326, gnomAD 0.05%). This missense change has been observed in individual(s) with Cockayne syndrome (PMID: 14661080, 32048102). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1718). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ERCC8 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects ERCC8 function (PMID: 16949367, 29531219). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000059650 SCV001820441 pathogenic not provided 2024-11-07 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect (PMID: 29531219); 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: 17084038, 14661080, 23571135, 28333167, 16865293, 25653723, 19894250, 32048102, 29531219, Guo2024_Paper, 37751047, 16949367)
Fulgent Genetics, Fulgent Genetics RCV005031380 SCV005673544 likely pathogenic Cockayne syndrome type 1; UV-sensitive syndrome 2 2024-06-24 criteria provided, single submitter clinical testing
OMIM RCV000001788 SCV000021944 pathogenic Cockayne syndrome type 1 2004-01-01 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000059650 SCV000091220 not provided not provided no assertion provided not provided
Counsyl RCV000001788 SCV000800534 uncertain significance Cockayne syndrome type 1 2017-05-12 flagged submission clinical testing

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