ClinVar Miner

Submissions for variant NM_004628.5(XPC):c.2074A>T (p.Lys692Ter)

gnomAD frequency: 0.00004  dbSNP: rs374117852
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589424 SCV000698490 pathogenic Xeroderma pigmentosum 2017-04-06 criteria provided, single submitter clinical testing Variant summary: The XPC c.2074A>T (p.Lys692*) variant results in a premature termination codon, predicted to cause a truncated or absent XPC protein due to nonsense mediated decay, which are commonly known mechanisms for disease. These predictions were confirmed by Khan et al (2006) who showed severely reduced level of mRNA and lack of protein expression in in vitro assay. This variant was found in 1/108904 control chromosomes at a frequency of 0.0000092, which does not exceed the estimated maximal expected allele frequency of a pathogenic XPC variant (0.0014142). This variant has been reported in at least two unrelated patients with Xeroderma Pigmentosum (Khan_2006, Kuschal_2013). In addition, truncation variants downstream of this position, such as c.2152C>T (p.R718*), c.2262delC (p.Asn754Lysfs) and c.2251-1G>C have been classified as "Pathogenic" by reputable databases/diagnostic laboratories . Taken together, this variant is classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001390105 SCV001591727 pathogenic not provided 2024-04-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys692*) in the XPC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in XPC are known to be pathogenic (PMID: 23173980, 25256075). This variant is present in population databases (rs374117852, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with xeroderma pigmentosum (PMID: 16081512). ClinVar contains an entry for this variant (Variation ID: 496267). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000666668 SCV004206998 pathogenic Xeroderma pigmentosum, group C 2024-03-27 criteria provided, single submitter clinical testing
Counsyl RCV000666668 SCV000790997 likely pathogenic Xeroderma pigmentosum, group C 2017-04-18 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.