ClinVar Miner

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

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
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
CSER_CC_NCGL; University of Washington Medical Center RCV000210904 SCV000264609 likely benign Colorectal cancer 2015-11-01 criteria provided, single submitter research
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.
Counsyl RCV000233156 SCV000488841 likely benign Colorectal cancer, susceptibility to, 12 2016-07-06 criteria provided, single submitter clinical testing
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
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.
Integrated Genetics/Laboratory Corporation of America RCV000432993 SCV000698662 likely benign not provided 2017-08-09 criteria provided, single submitter clinical testing Variant summary: The POLE c.16G>C (p.Gly6Arg) variant involves the alteration of a non-conserved nucleotide, resulting in a missense change that does not lie within a known functional domain (InterPro). 4/5 in silico tools predict a benign outcome for this variant. This variant was found in the large control database gnomAD at a frequency of 0.0025771 (353/136976 control chromosomes; 2 homozygotes), which is approximately 181 times the estimated maximal expected allele frequency of a pathogenic POLE variant (0.0000142), strongly suggesting this variant is likely a benign polymorphism. The variant has been identified in one patient with colorectal cancer without strong evidence for or against pathogenicity (Kothari_Cancer_2016). In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant with conflicting interpretations in ClinVar including uncertain significance (1x), likely benign (4x), and benign (1x). Due to the high frequency and homozygosity in the general population, this variant is classified as likely benign.
Invitae RCV000233156 SCV000289265 benign Colorectal cancer, susceptibility to, 12 2018-01-09 criteria provided, single submitter clinical testing
PreventionGenetics RCV000432993 SCV000806726 likely benign not provided 2017-02-20 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000202795 SCV000601985 likely benign not specified 2017-04-17 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
True Health Diagnostics RCV000568177 SCV000788161 likely benign Hereditary cancer-predisposing syndrome 2017-12-01 no assertion criteria provided clinical testing

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