ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.1596C>T (p.Ala532=)

gnomAD frequency: 0.00009  dbSNP: rs550441767
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000477152 SCV000522012 likely benign not provided 2021-01-22 criteria provided, single submitter clinical testing
Invitae RCV000990256 SCV000558680 likely benign Colorectal cancer, susceptibility to, 10 2024-01-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV000573167 SCV000670959 likely benign Hereditary cancer-predisposing syndrome 2015-07-02 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Mendelics RCV000990256 SCV001141144 likely benign Colorectal cancer, susceptibility to, 10 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000477152 SCV001152026 likely benign not provided 2022-04-01 criteria provided, single submitter clinical testing POLD1: BP4, BP7
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000434434 SCV001362684 benign not specified 2019-01-18 criteria provided, single submitter clinical testing Variant summary: POLD1 c.1596C>T results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 6.9e-05 in 276638 control chromosomes (gnomAD). The observed variant frequency is approximately 5-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in POLD1 causing Colorectal Cancer phenotype (1.4e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1596C>T in individuals affected with Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Sema4, Sema4 RCV000573167 SCV002534597 likely benign Hereditary cancer-predisposing syndrome 2021-06-17 criteria provided, single submitter curation

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