ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.2106G>T (p.Gly702=) (rs5744801)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001079677 SCV000289289 benign Colorectal cancer, susceptibility to, 12 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000444253 SCV000521366 likely benign not specified 2018-02-02 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.
Ambry Genetics RCV000572802 SCV000671308 likely benign Hereditary cancer-predisposing syndrome 2015-08-12 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000444253 SCV000806740 benign not specified 2017-08-11 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759273 SCV000888508 benign not provided 2018-09-11 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000444253 SCV001361240 benign not specified 2019-04-25 criteria provided, single submitter clinical testing Variant summary: POLE c.2106G>T alters a non-conserved nucleotide resulting in a synonymous change. 4/5 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 0.00055 in 250120 control chromosomes, predominantly at a frequency of 0.0074 within the African or African-American subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 521 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 or African-American origin. To our knowledge, no occurrence of c.2106G>T in individuals affected with Colorectal Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Six submitters have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (2x) /likely benign (4x). Based on the evidence outlined above, the variant was classified as benign.
True Health Diagnostics RCV000572802 SCV000805294 likely benign Hereditary cancer-predisposing syndrome 2018-04-27 no assertion criteria provided clinical testing

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