Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000471600 | SCV000547502 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2020-03-11 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 4 of the POLD1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Missense variants that disrupt the 3'-5' exonuclease (proof-reading) activity of the POLD1 protein, are associated with an increased risk for colonic adenomatous polyps and colon cancer (PMID: 23263490, 23447401). However loss-of-function variants, which result in an absent or severely disrupted POLD1 protein, and missense variants outside the exonuclease domain are unlikely to be associated with polyposis or colon cancer. Without further clinical and genetic evidence, this variant has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with POLD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 407958). This variant is not present in population databases (ExAC no frequency). |