ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.5679-3C>T

dbSNP: rs1555221512
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000549313 SCV000653392 uncertain significance Colorectal cancer, susceptibility to, 12 2022-03-01 criteria provided, single submitter clinical testing This sequence change falls in intron 41 of the POLE gene. It does not directly change the encoded amino acid sequence of the POLE protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 473756). 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. 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.
Mendelics RCV000549313 SCV001138862 likely benign Colorectal cancer, susceptibility to, 12 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV001024394 SCV001186404 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-02 criteria provided, single submitter clinical testing The c.5679-3C>T intronic variant results from a C to T substitution 3 nucleotides upstream from coding exon 42 in the POLE gene. This nucleotide position is poorly conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted by ESEfinder to weaken the efficiency of the native splice acceptor site, but is not predicted to have a deleterious effect on this splice acceptor site by BDGP; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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