ClinVar Miner

Submissions for variant NM_000400.4(ERCC2):c.1354C>T (p.Gln452Ter)

gnomAD frequency: 0.00002  dbSNP: rs199643821
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001942186 SCV002236342 pathogenic not provided 2024-10-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln452*) in the ERCC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ERCC2 are known to be pathogenic (PMID: 9238033, 11335038, 19085937, 19934020). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with xeroderma pigmentosum (PMID: 19934020, 32047639). ClinVar contains an entry for this variant (Variation ID: 1455083). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects ERCC2 function (PMID: 19934020). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001942186 SCV004034784 pathogenic not provided 2023-03-07 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Published functional studies demonstrate that this variant impairs DNA repair activities, transcription activity, and transactivation mediated by nuclear receptors (PMID: 19934020); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 34426522, 31263571, 33084842, 19934020, 32047639)
Baylor Genetics RCV003471163 SCV004194670 pathogenic Cerebrooculofacioskeletal syndrome 2 2024-01-16 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005016946 SCV005648406 pathogenic Cerebrooculofacioskeletal syndrome 2; Xeroderma pigmentosum, group D; Trichothiodystrophy 1, photosensitive 2024-04-25 criteria provided, single submitter clinical testing

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.