ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.1548C>T (p.Ala516=)

gnomAD frequency: 0.04514  dbSNP: rs2230247
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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000427134 SCV000518894 benign not specified 2015-11-13 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000459453 SCV000558778 benign Colorectal cancer, susceptibility to, 10 2024-02-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000569706 SCV000670878 benign Hereditary cancer-predisposing syndrome 2015-05-20 criteria provided, single submitter clinical testing This alteration is classified as 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589154 SCV000697992 benign not provided 2016-05-19 criteria provided, single submitter clinical testing Variant summary: The POLD1 c.1548C>T (p.Ala516Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant does not affect any ESE site. This variant was found in 1638/120504 control chromosomes (117 homozygotes) at a frequency of 0.0135929, which is approximately 957 times the estimated maximal expected allele frequency of a pathogenic POLD1 variant (0.0000142), suggesting this variant is likely a benign polymorphism. Taken together, this variant is classified as benign.
Preventiongenetics, part of Exact Sciences RCV000427134 SCV000806467 benign not specified 2016-12-06 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000427134 SCV000889650 benign not specified 2020-08-10 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000427134 SCV002551918 benign not specified 2023-08-15 criteria provided, single submitter clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV000459453 SCV004016627 benign Colorectal cancer, susceptibility to, 10 2023-07-07 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000569706 SCV000788129 likely benign Hereditary cancer-predisposing syndrome 2017-10-25 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001354613 SCV001549270 benign Carcinoma of colon no assertion criteria provided clinical testing The POLD1 p.Ala516= variant was identified in dbSNP (ID: rs2230247) “With Benign allele”, ClinVar (classified benign by GeneDx, Invitae, Ambry Genetics and Quest Diagnostics Nichols Institute San Juan Capistrano), and in control databases in 3896 (256 homozygous) of 276142 chromosomes at a frequency of 0.01 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 3408 (250 homozygous) of 23952 chromosomes (freq: 0.14), Other in 42 of 6448 chromosomes (freq: 0.007), Latino in 328 (5 homozygous) of 34418 chromosomes (freq: 0.01), European Non-Finnish in 77 (1 homozygous) of 125860 chromosomes (freq: 0.0006), Ashkenazi Jewish in 32 of 10134 chromosomes (freq: 0.003), and South Asian in 9 of 30778 chromosomes (freq: 0.0003), while not observed in the East Asian and European Finnish populations. The p.Ala516= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000427134 SCV001809249 benign not specified no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000427134 SCV001922862 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000427134 SCV001951120 benign not specified no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000427134 SCV002036976 benign not specified no assertion criteria provided clinical testing

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