Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV000018275 | SCV002583758 | pathogenic | Trichothiodystrophy 1, photosensitive | 2022-07-20 | criteria provided, single submitter | clinical testing | PS3 PM3_Strong PM2 |
| 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, |
RCV003153304 | SCV003843680 | likely pathogenic | Ovarian cancer | 2022-01-01 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003460483 | SCV004194611 | likely pathogenic | Cerebrooculofacioskeletal syndrome 2 | 2024-03-24 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000018275 | SCV000038554 | pathogenic | Trichothiodystrophy 1, photosensitive | 2001-03-01 | no assertion criteria provided | literature only |