ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.68A>G (p.Asp23Gly)

gnomAD frequency: 0.00001  dbSNP: rs765898876
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001534278 SCV000653466 uncertain significance not provided 2025-01-17 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 23 of the POLE protein (p.Asp23Gly). This variant is present in population databases (rs765898876, gnomAD 0.006%). 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: 473820). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Fulgent Genetics, Fulgent Genetics RCV000763825 SCV000894742 uncertain significance Colorectal cancer, susceptibility to, 12; Facial dysmorphism-immunodeficiency-livedo-short stature syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV001534278 SCV001751194 uncertain significance not provided 2024-07-19 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 29056344)
Sema4, Sema4 RCV002257835 SCV002536934 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-20 criteria provided, single submitter curation
Ambry Genetics RCV002257835 SCV002662959 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-10 criteria provided, single submitter clinical testing The p.D23G variant (also known as c.68A>G), located in coding exon 2 of the POLE gene, results from an A to G substitution at nucleotide position 68. The aspartic acid at codon 23 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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