ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.317-3C>G

dbSNP: rs1601198088
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000800511 SCV000940230 uncertain significance Colorectal cancer, susceptibility to, 10 2018-10-04 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with POLD1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 3 of the POLD1 gene. It does not directly change the encoded amino acid sequence of the POLD1 protein, but it affects a nucleotide within the consensus splice site of the intron.
Ambry Genetics RCV001018971 SCV001180271 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-20 criteria provided, single submitter clinical testing The c.317-3C>G intronic variant results from a C to G substitution 3 nucleotides upstream from coding exon 3 in the POLD1 gene. This nucleotide position is well conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted by BDGP to abolish the native splice acceptor site, but is predicted to weaken (but not abolish) the efficiency of the native splice acceptor site by ESEfinder; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001772063 SCV001992946 uncertain significance not provided 2019-06-24 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge

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