ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.6817A>T (p.Thr2273Ser) (rs73481453)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000231258 SCV000289485 benign Colorectal cancer, susceptibility to, 12 2019-12-31 criteria provided, single submitter clinical testing
Counsyl RCV000231258 SCV000489041 benign Colorectal cancer, susceptibility to, 12 2016-08-05 criteria provided, single submitter clinical testing
GeneDx RCV000426951 SCV000518897 likely benign not specified 2018-01-18 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000426951 SCV000602093 benign not specified 2017-06-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV000562384 SCV000671243 benign Hereditary cancer-predisposing syndrome 2015-06-04 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000426951 SCV000806850 benign not specified 2016-12-30 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000760039 SCV000889789 benign not provided 2017-06-07 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000426951 SCV000920074 benign not specified 2018-08-27 criteria provided, single submitter clinical testing Variant summary: POLE c.6817A>T (p.Thr2273Ser) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0015 in 276634 control chromosomes, predominantly at a frequency of 0.016 within the African subpopulation in the gnomAD database, including 5 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 1126 fold of the estimated maximal expected allele frequency for a pathogenic variant in POLE causing Colorectal Cancer phenotype (1.4e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.6817A>T in individuals affected with Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Six 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/likely benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000426951 SCV001158157 benign not specified 2019-02-06 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000562384 SCV000788193 likely benign Hereditary cancer-predisposing syndrome 2017-09-11 no assertion criteria provided clinical testing

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