ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.6747+5G>A

dbSNP: rs1555300791
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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 RCV000561128 SCV000671349 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-31 criteria provided, single submitter clinical testing The c.6747+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 48 in the POLE gene. This nucleotide position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003539956 SCV000772692 uncertain significance not provided 2025-01-30 criteria provided, single submitter clinical testing This sequence change falls in intron 48 of the POLE gene. It does not directly change the encoded amino acid sequence of the POLE protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. 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: 484444). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 48, but is expected to preserve the integrity of the reading-frame (internal data). 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 RCV000709236 SCV000838667 uncertain significance Familial colorectal cancer 2018-07-02 criteria provided, single submitter clinical testing

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