ClinVar

Description

Variant summary: The variant identified by MLPA or other technology involves the deletion of exons 4-5 in the POLH gene. A presumed nomenclature of c.(272+1_273-1)_(660+1_661-1)del has been designated for the purposes of this classification. Although exact breakpoints of this deletion are not known, it is expected to result in a frameshift in the POLH gene, a known mechanism of disease. The variant was absent in 21668 control chromosomes (gnomAD Structural Variants dataset). To our knowledge, no occurrence of c.(272+1_273-1)_(660+1_661-1)del in individuals affected with Xeroderma Pigmentosum and no experimental evidence demonstrating its impact on protein function have been reported. Deletion of exon 5, which is also expected to cause a frameshift in the POLH gene, has been catagorized as disease causing in HGMD (accession: CG024995). 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 likely pathogenic.