Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000001049 | SCV000794422 | pathogenic | Xeroderma pigmentosum group A | 2017-09-26 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780797 | SCV000918359 | pathogenic | Xeroderma pigmentosum | 2018-05-11 | criteria provided, single submitter | clinical testing | Variant summary: XPA c.349_353delCTTAT (p.Leu117GlufsX4) 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 7.2e-06 in 276628 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in XPA causing Xeroderma Pigmentosum (7.2e-06 vs 1.60e-03), allowing no conclusion about variant significance. The variant, c.349_353delCTTAT, has been reported in the literature in individuals affected with Xeroderma Pigmentosum (Ghafouri-Fard_2016, Christen-Zaech_2009, States_1998) where it was found to co-segregate with disease. These data indicate that the variant is likely to be associated with disease. At-least one study reports a hypersensitivity of patient derived fibroblasts to the killing effects of UV radiation, although quantitative data were not provided by the authors. 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. |
| Labcorp Genetics |
RCV001057886 | SCV001222407 | pathogenic | not provided | 2023-11-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu117Glufs*4) in the XPA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in XPA are known to be pathogenic (PMID: 27607234). This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with xeroderma pigmentosum (PMID: 1339397, 19917958). ClinVar contains an entry for this variant (Variation ID: 994). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV000001049 | SCV003821872 | pathogenic | Xeroderma pigmentosum group A | 2023-12-15 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000001049 | SCV004206949 | pathogenic | Xeroderma pigmentosum group A | 2024-02-08 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000001049 | SCV000021199 | pathogenic | Xeroderma pigmentosum group A | 1992-03-01 | no assertion criteria provided | literature only |