ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.2955G>T (p.Arg985=)

gnomAD frequency: 0.00019  dbSNP: rs770495723
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001082258 SCV000287603 benign Colorectal cancer, susceptibility to, 10 2024-02-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000563576 SCV000670914 likely benign Hereditary cancer-predisposing syndrome 2015-11-01 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
GeneDx RCV000679506 SCV000714163 likely benign not provided 2020-05-04 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000679506 SCV000806517 likely benign not provided 2017-12-11 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000606071 SCV001362688 benign not specified 2019-10-04 criteria provided, single submitter clinical testing Variant summary: POLD1 c.2955G>T (p.Arg985Arg) alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 0.00064 in 164594 control chromosomes. The observed variant frequency is approximately 45 fold of 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.2955G>T in individuals affected with Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (n=1)/likely benign(n=3). Based on the evidence outlined above, the variant was classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000606071 SCV001469870 benign not specified 2019-10-18 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000679506 SCV004562336 benign not provided 2023-02-07 criteria provided, single submitter clinical testing

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