ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.2938G>A (p.Glu980Lys)

gnomAD frequency: 0.00003  dbSNP: rs373389672
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000541764 SCV000646615 uncertain significance Colorectal cancer, susceptibility to, 10 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 980 of the POLD1 protein (p.Glu980Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with POLD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 469311). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759234 SCV000888458 uncertain significance not provided 2017-11-10 criteria provided, single submitter clinical testing
GeneDx RCV000759234 SCV001827086 uncertain significance not provided 2023-07-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002438441 SCV002748613 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-12 criteria provided, single submitter clinical testing The p.E980K variant (also known as c.2938G>A), located in coding exon 22 of the POLD1 gene, results from a G to A substitution at nucleotide position 2938. The glutamic acid at codon 980 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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