Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000666956 | SCV000791333 | likely pathogenic | Xeroderma pigmentosum group A | 2017-05-09 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781923 | SCV000920349 | pathogenic | Xeroderma pigmentosum | 2018-11-29 | criteria provided, single submitter | clinical testing | Variant summary: XPA c.631C>T (p.Arg211X) 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 4.1e-06 in 245906 control chromosomes (gnomAD). c.631C>T has been reported in the literature in multiple homozygote and compound heterozygote individuals affected with Xeroderma Pigmentosum (Satokata_1992, Zhou_2017). These data indicate that the variant is very likely to be associated with disease. A functional study indicates that the variant would "cause instability of the XPAC mRNA and loss of repair activity of the XPAC protein." (Satokata_1992) A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cties the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV001045901 | SCV001209776 | pathogenic | not provided | 2024-01-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg211*) in the XPA gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 63 amino acid(s) of the XPA protein. This variant is present in population databases (rs149226993, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with xeroderma pigmentosum (PMID: 1372103, 27607234). ClinVar contains an entry for this variant (Variation ID: 551809). This variant disrupts a region of the XPA protein in which other variant(s) (p.Arg228*) have been determined to be pathogenic (PMID: 8105686, 9671271, 24135642, 27607234). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001045901 | SCV002584370 | pathogenic | not provided | 2022-04-06 | criteria provided, single submitter | clinical testing | Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 63 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 1372103, 15214909, 31350202, 27607234) |
| Baylor Genetics | RCV000666956 | SCV004206939 | pathogenic | Xeroderma pigmentosum group A | 2023-10-30 | criteria provided, single submitter | clinical testing |