Submissions for variant NM_004628.5(XPC):c.2250+1G>A

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV002280586	SCV004814137	pathogenic	Xeroderma pigmentosum, group C	2022-03-04	criteria provided, single submitter	clinical testing	The XPC c.2250+1G>A variant results in a substitution at the consensus splice donor site, which is predicted to result in splicing defects that may lead to a truncated protein. To our knowledge, this variant has not been reported in the peer-reviewed literature. This variant is reported in the Genome Aggregation Database in one allele at a frequency of 0.000033 in the South Asian population (version 3.1.2). This variant was identified in a homozygous state in the proband with a phenotype consistent with xeroderma pigmentosum. Based on the available evidence, the c.2250+1G>A variant is classified as pathogenic for xeroderma pigmentosum.
Hacettepe Pediatric Genetics Laboratory, Hacettepe University	RCV002280586	SCV002099535	pathogenic	Xeroderma pigmentosum, group C	2022-02-25	no assertion criteria provided	clinical testing	The variant detected in homozygous state in the XPC gene, c.2250+1G>A, is a splice site mutation (splice donor site mutation). It is associated with the phenotype called "Xeroderma pigmentosum, group C". It has not been reported in ClinVar before, and it is suggested to be a pathogenic variant. This variant was neither found in ExAC nor 1000G. This change was classified as “pathogenic” according to the ACMG guidelines and predicted to be disease causing by in silico analysis such as MutationTaster.