ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.1494+4C>G

gnomAD frequency: 0.00001  dbSNP: rs1484829299
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001011859 SCV001172233 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-07 criteria provided, single submitter clinical testing The c.1494+4C>G intronic variant results from a C to G substitution 4 nucleotides after coding exon 11 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 weaken the efficiency of the native splice donor site, but is not predicted to have a deleterious effect on this splice donor site by ESEfinder; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001220633 SCV001392636 uncertain significance Colorectal cancer, susceptibility to, 10 2023-02-03 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. Variants that disrupt 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 is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 819364). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change falls in intron 12 of the POLD1 gene. It does not directly change the encoded amino acid sequence of the POLD1 protein. It affects a nucleotide within the consensus splice site.
PreventionGenetics, part of Exact Sciences RCV003973027 SCV004798175 likely benign POLD1-related condition 2021-12-23 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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