ClinVar Miner

Submissions for variant NM_000124.4(ERCC6):c.1738C>T (p.Gln580Ter)

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Total submissions: 2
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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 RCV003155870 SCV003845151 likely pathogenic Cerebrooculofacioskeletal syndrome 1 2023-02-24 criteria provided, single submitter clinical testing Variant summary: ERCC6 c.1738C>T (p.Gln580X) 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 reported in HGMD in association with Cockayne syndrome and Cerebro-oculo-facio-skeletal syndrome. The variant was absent in 251378 control chromosomes. To our knowledge, no occurrence of c.1738C>T in individuals affected with Cerebrooculofacioskeletal Syndrome 1 and no experimental evidence demonstrating its impact on protein function have 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003679164 SCV004407932 pathogenic not provided 2023-10-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln580*) in the ERCC6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ERCC6 are known to be pathogenic (PMID: 18628313, 29572252). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ERCC6-related conditions. ClinVar contains an entry for this variant (Variation ID: 2445951). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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