ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.16G>C (p.Gly6Arg) (rs202220778)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000202795 SCV000258038 likely benign not specified 2015-07-22 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000210904 SCV000264609 likely benign Colorectal cancer 2015-11-01 criteria provided, single submitter research
Invitae RCV000432993 SCV000289265 benign not provided 2019-03-06 criteria provided, single submitter clinical testing
Counsyl RCV000233156 SCV000488841 likely benign Colorectal cancer, susceptibility to, 12 2016-07-06 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000432993 SCV000511481 uncertain significance not provided 2016-11-10 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
GeneDx RCV000202795 SCV000518043 likely benign not specified 2017-12-07 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 RCV000202795 SCV000601985 likely benign not specified 2017-04-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV000568177 SCV000671367 benign Hereditary cancer-predisposing syndrome 2015-06-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance,Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene,Other data supporting benign classification,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Integrated Genetics/Laboratory Corporation of America RCV000202795 SCV000698662 benign not specified 2019-08-05 criteria provided, single submitter clinical testing Variant summary: POLE c.16G>C (p.Gly6Arg) results in a non-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 0.0027 in 110214 control chromosomes, predominantly at a frequency of 0.0045 within the Non-Finnish European subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 317 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 Non-Finnish European origin. c.16G>C has been reported in the literature in individuals affected with Colorectal Cancer (ex Kothari_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Colorectal Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Ten clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Nine of these ten have classified the variant as benign (n=3)/likely benign (n=6). Based on the evidence outlined above, the variant was re-evaluated as benign.
PreventionGenetics,PreventionGenetics RCV000432993 SCV000806726 likely benign not provided 2017-02-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000432993 SCV000889712 benign not provided 2018-04-17 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000432993 SCV001148917 likely benign not provided 2019-02-01 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000568177 SCV000788161 likely benign Hereditary cancer-predisposing syndrome 2017-12-01 no assertion criteria provided clinical testing

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