Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Claritas Genomics | RCV000170373 | SCV000222788 | likely pathogenic | Cockayne syndrome type 2 | 2013-10-21 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000667169 | SCV000791576 | likely pathogenic | DE SANCTIS-CACCHIONE SYNDROME; Cerebrooculofacioskeletal syndrome 1; Cockayne syndrome type 2 | 2017-05-12 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001227175 | SCV001399519 | pathogenic | not provided | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg652*) 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 present in population databases (rs767247987, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Cockayne syndrome (PMID: 19894250, 29572252). ClinVar contains an entry for this variant (Variation ID: 190155). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003491926 | SCV004241529 | pathogenic | Cockayne syndrome | 2023-12-15 | criteria provided, single submitter | clinical testing | Variant summary: ERCC6 c.1954C>T (p.Arg652X) 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. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.6e-05 in 251240 control chromosomes. c.1954C>T has been reported in the literature in individuals affected with Cockayne Syndrome. These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 19894250). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |