ClinVar Miner

Submissions for variant NM_000124.4(ERCC6):c.229C>T (p.Arg77Ter)

gnomAD frequency: 0.00001  dbSNP: rs121917903
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000502276 SCV000594584 pathogenic Cockayne syndrome type 2 2015-10-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001851562 SCV002247389 pathogenic not provided 2023-07-16 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 1708). This premature translational stop signal has been observed in individual(s) with clinical features of Cockayne syndrome (PMID: 15486090, 30111349). This variant is present in population databases (rs121917903, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg77*) 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). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003230340 SCV003928793 pathogenic Cockayne syndrome 2023-04-15 criteria provided, single submitter clinical testing Variant summary: ERCC6 c.229C>T (p.Arg77X) results in a premature termination codon and is confirmed to cause absence of the protein (Horibata_2011), which is a commonly known mechanism for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 251438 control chromosomes (gnomAD). c.229C>T has been reported in the literature as a biallelic genotype in multiple individuals affected with UV-sensitive syndrome (Horibata_2004, Horibata_2011), and Cockayne syndrome (Tonduti_2018, Sun_2019). These data indicate that the variant is very likely to be associated with disease. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000001777 SCV000021933 pathogenic UV-sensitive syndrome 1 2012-05-01 no assertion criteria provided literature only

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