ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.1473+2T>C

dbSNP: rs1593072081
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001011771 SCV001172131 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-22 criteria provided, single submitter clinical testing The c.1473+2T>C intronic variant results from a T to C substitution two nucleotides after coding exon 14 in the POLE gene. This nucleotide position is highly conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted by BDGP to abolish the native splice donor site, but is predicted to weaken (but not abolish) the efficiency of the native splice donor site by ESEfinder; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, loss of function via haploinsufficiency in POLE has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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