ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.1020+5_1020+6delinsAA (rs1064795707)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485457 SCV000571769 likely benign not specified 2016-09-22 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV001009725 SCV001169825 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-21 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV001060272 SCV001224949 uncertain significance Colorectal cancer, susceptibility to, 12 2019-08-08 criteria provided, single submitter clinical testing This sequence change falls in intron 10 of the POLE gene. It does not directly change the encoded amino acid sequence of the POLE protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is reported as two separate entries in the ExAC population database (c.1020+6G>A, ExAC 0.03% and c.1020+5G>A, ExAC 0.03%). This variant has not been reported in the literature in individuals with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 422325). 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. 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.

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