ClinVar Miner

Submissions for variant NM_004628.5(XPC):c.566_567del (p.Tyr189fs)

dbSNP: rs752088918
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589161 SCV000698493 pathogenic Xeroderma pigmentosum 2017-07-20 criteria provided, single submitter clinical testing Variant summary: The c.566_567delAT (p.Tyr189Serfs) variant in XPC gene is a frameshift change predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. These predictions were confirmed by Northern blot analysis that has revealed greatly reduced xeroderma pigmentosum complementation group C mRNA as well as reductions in post-ultraviolet survival rate, unscheduled DNA synthesis, global genome DNA repair deficiency and aborted plasmid host cell reactivation (Slor ,2000). The variant is present in the large control population dataset of ExAC at a low frequency 0.00004 (5/113986 chrs tested), exclusively in individuals of European descent (0.000079; 5/63374 chrs tested) which does not exceed the maximal expected frequency of a pathogenic allele (0.0014) in this gene. The variant of interest has been reported homozygously in at least 3 XP-C patients. The c.566_567delAT is cited as Pathogenic by reputable database/diagnostic center. Taken together, the variant was classified as Pathogenic.
Counsyl RCV000000282 SCV000789545 pathogenic Xeroderma pigmentosum, group C 2017-02-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001062453 SCV001227254 pathogenic not provided 2024-07-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr189Serfs*10) 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 (rs752088918, gnomAD 0.06%). This premature translational stop signal has been observed in individual(s) with xeroderma pigmentosum (PMID: 11121128). It has also been observed to segregate with disease in related individuals. This variant is also known as c.669_670delAT. ClinVar contains an entry for this variant (Variation ID: 258). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000000282 SCV004206972 pathogenic Xeroderma pigmentosum, group C 2024-03-19 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000000282 SCV005656588 pathogenic Xeroderma pigmentosum, group C 2024-03-30 criteria provided, single submitter clinical testing
OMIM RCV000000282 SCV000020426 pathogenic Xeroderma pigmentosum, group C 2000-12-01 no assertion criteria provided literature only

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