Submissions for variant NM_000400.4(ERCC2):c.373C>T (p.Arg125Cys)

gnomAD frequency: 0.00007  dbSNP: rs372425466

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001900953	SCV002158713	uncertain significance	not provided	2022-09-16	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 125 of the ERCC2 protein (p.Arg125Cys). This variant is present in population databases (rs372425466, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with ERCC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1394650). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Sema4, Sema4	RCV002259151	SCV002531598	uncertain significance	Xeroderma pigmentosum	2021-09-08	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV001900953	SCV004702174	uncertain significance	not provided	2024-01-01	criteria provided, single submitter	clinical testing	ERCC2: PM2:Supporting, PP3