ClinVar Miner

Submissions for variant NM_000400.4(ERCC2):c.195_196delinsTT (p.Glu66Ter)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002281878 SCV002572448 likely pathogenic Xeroderma pigmentosum 2022-08-31 criteria provided, single submitter clinical testing Variant summary: ERCC2 c.195_196delinsTT (p.Glu66X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4.8e-05 in 251490 control chromosomes. c.195_196delinsTT has been reported in the literature in one individuals affected with uterine corpus endometrial carcinoma. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics RCV003471309 SCV004194633 likely pathogenic Cerebrooculofacioskeletal syndrome 2 2023-09-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003728067 SCV004520638 pathogenic not provided 2023-05-14 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1705248). This variant has not been reported in the literature in individuals affected with ERCC2-related conditions. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change creates a premature translational stop signal (p.Glu66*) 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).

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