Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000483815 | SCV000569255 | uncertain significance | not provided | 2016-11-01 | criteria provided, single submitter | clinical testing | This variant is denoted POLD1 c.1893-6A>G or IVS15-6A>G and consists of an A>G nucleotide substitution at the -6 position of intron 15 of the POLD1 gene. Multiple in silico models predict this variant to destroy the nearby natural splice acceptor site or create a cryptic splice site and to possibly cause abnormal gene splicing. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. POLD1 c.1893-6A>G was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. The adenine (A) nucleotide that is altered is not conserved across species. Based on currently available evidence, it is unclear whether POLD1 c.1893-6A>G is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Invitae | RCV000645870 | SCV000767625 | uncertain significance | Colorectal cancer, susceptibility to, 10 | 2021-10-02 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 420425). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 15 of the POLD1 gene. It does not directly change the encoded amino acid sequence of the POLD1 protein. |