Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000668799 | SCV000793459 | uncertain significance | Xeroderma pigmentosum group A | 2017-08-16 | criteria provided, single submitter | clinical testing | |
| Sema4, |
RCV002256462 | SCV002531510 | likely pathogenic | Xeroderma pigmentosum | 2021-12-29 | criteria provided, single submitter | curation | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002256462 | SCV004039386 | likely pathogenic | Xeroderma pigmentosum | 2023-08-01 | criteria provided, single submitter | clinical testing | Variant summary: XPA c.378T>G (p.Cys126Trp) results in a non-conservative amino acid change located in the zinc finger domain (IPR022652), affecting a zinc-coordinating Cys residue (PMID 9078375) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250836 control chromosomes (gnomAD). c.378T>G has been reported in the literature in at least one homozygous individual affected with Xeroderma Pigmentosum (Tamhankar_2015). These data indicate that the variant may be associated with disease. At least one publication reported experimental evidence evaluating an impact on protein function, and demonstrated that the variant drastically reduces nucleotide excision repair (NER) in a cell-based NER activity assay (Blee_2022). The following publications have been ascertained in the context of this evaluation (PMID: 35687855, 25566891). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as likely pathogenic, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic. |