ClinVar Miner

Submissions for variant NM_000400.4(ERCC2):c.1972C>T (p.Arg658Cys)

gnomAD frequency: 0.00004  dbSNP: rs121913021
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV000018275 SCV002583758 pathogenic Trichothiodystrophy 1, photosensitive 2022-07-20 criteria provided, single submitter clinical testing PS3 PM3_Strong PM2
Fulgent Genetics, Fulgent Genetics RCV002482884 SCV002799317 likely pathogenic Cerebrooculofacioskeletal syndrome 2; Xeroderma pigmentosum, group D; Trichothiodystrophy 1, photosensitive 2022-05-25 criteria provided, single submitter clinical testing
Invitae RCV002513098 SCV003443340 likely pathogenic not provided 2023-09-12 criteria provided, single submitter clinical testing This variant disrupts the p.Arg658 amino acid residue in ERCC2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8571952, 9238033, 11585917, 12820975, 25431422). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. Experimental studies have shown that this missense change affects ERCC2 function (PMID: 12820975, 25431422). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 658 of the ERCC2 protein (p.Arg658Cys). This variant is present in population databases (rs121913021, gnomAD 0.01%). This missense change has been observed in individuals with trichothiodystrophy (PMID: 8571952, 11242112). ClinVar contains an entry for this variant (Variation ID: 16785). 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.
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University RCV003153304 SCV003843680 likely pathogenic Ovarian cancer 2022-01-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV003460483 SCV004194611 likely pathogenic Cerebrooculofacioskeletal syndrome 2 2023-10-31 criteria provided, single submitter clinical testing
OMIM RCV000018275 SCV000038554 pathogenic Trichothiodystrophy 1, photosensitive 2001-03-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.