Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001375592 | SCV001572492 | pathogenic | Xeroderma pigmentosum | 2021-04-02 | criteria provided, single submitter | clinical testing | Variant summary: ERCC5 c.2606_2607delTG (p.Val869GlyfsX11) 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. The variant allele was found at a frequency of 3.2e-05 in 31392 control chromosomes (gnomAD). c.2606_2607delTG (also reported as c.2801_2804delTG) has been reported in the literature in an individual who was compound heterozygous for the variant of interest and another nonsense variant (Emmert_2002). The variant has been subsequently cited by others (example: Chikhaoui_2019, Drury_2014, Schafer_2013). The patient mentioned above was presented with combined features of Xeroderma Pigmentosum (XP) and Cockayne syndrome (CS). Fibroblasts derived from this patient showed marked reduction in post-ultraviolet cell survival and DNA repair (Emmert_2002). 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 pathogenic. |
Gene |
RCV003229893 | SCV003927730 | pathogenic | not provided | 2022-12-07 | criteria provided, single submitter | clinical testing | Frameshift 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; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24700531, 12060391) |