ClinVar Miner

Submissions for variant NM_006231.3(POLE):c.6495C>T (p.Arg2165=) (rs114778730)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001084235 SCV000289462 benign Colorectal cancer, susceptibility to, 12 2020-12-06 criteria provided, single submitter clinical testing
GeneDx RCV000679664 SCV000521140 likely benign not provided 2020-10-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000575910 SCV000671254 likely benign Hereditary cancer-predisposing syndrome 2015-06-22 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
PreventionGenetics,PreventionGenetics RCV000679664 SCV000806839 likely benign not provided 2017-04-25 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679664 SCV000888568 benign not provided 2018-06-26 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001287304 SCV001473979 likely benign none provided 2020-07-24 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354477 SCV001549104 likely benign Carcinoma of colon no assertion criteria provided clinical testing The POLE p.Arg2165= variant was not identified in the literature nor was it identified in the Cosmic database. The variant was identified in dbSNP (ID: rs114778730) as "With Likely benign allele" and in ClinVar (classified as benign by Invitae; and as likely benign by GeneDx and Ambry Genetics). The variant was identified in control databases in 169 of 268900 chromosomes at a frequency of 0.0006 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 4 of 23124 chromosomes (freq: 0.0002), Other in 7 of 6322 chromosomes (freq: 0.001), Latino in 18 of 33610 chromosomes (freq: 0.0005), European in 121 of 122322 chromosomes (freq: 0.001), Finnish in 17 of 25164 chromosomes (freq: 0.0007), and South Asian in 2 of 29946 chromosomes (freq: 0.00007); it was not observed in the Ashkenazi Jewish or East Asian populations. The p.Arg2165= 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, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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