ClinVar

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 675 of the ERCC2 protein (p.Gly675Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of xeroderma pigmentosum (PMID: 7825573). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ERCC2 protein function. Experimental studies have shown that this missense change affects ERCC2 function (PMID: 12820975, 25431422). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.