Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194154 | SCV001363456 | pathogenic | Xeroderma pigmentosum | 2019-10-21 | criteria provided, single submitter | clinical testing | Variant summary: ERCC5 c.2751delA (p.Lys917AsnfsX65) 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 was absent in 248226 control chromosomes (gnomAD). c.2751delA has been reported in the literature in a compound heterozygous individual affected with Xeroderma pigmentosum (Lalle_2002). These data indicate that the variant is likely to be associated with disease. In functional studies, the cells transfected with the variant were highly UV sensitive compared to control cells (Lalle_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. |
| Invitae | RCV003556040 | SCV004296520 | pathogenic | not provided | 2023-07-19 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. For these reasons, this variant has been classified as Pathogenic. Studies have shown that this premature translational stop signal is associated with altered splicing resulting in multiple RNA products (PMID: 11841555). Experimental studies have shown that this premature translational stop signal affects ERCC5 function (PMID: 11841555). ClinVar contains an entry for this variant (Variation ID: 16576). This variant is also known as K917fs962fsX1186. This premature translational stop signal has been observed in individuals with clinical features of xeroderma pigmentosum (PMID: 11841555; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys917Asnfs*65) in the ERCC5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 270 amino acid(s) of the ERCC5 protein. |
| OMIM | RCV000018044 | SCV000038323 | pathogenic | Xeroderma pigmentosum, group G | 2002-02-01 | no assertion criteria provided | literature only |