ClinVar Miner

Submissions for variant NM_000038.6(APC):c.2204C>T (p.Ala735Val) (rs147655929)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131447 SCV000186431 benign Hereditary cancer-predisposing syndrome 2015-06-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene
GeneDx RCV000254627 SCV000209463 likely benign not specified 2017-08-29 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.
Invitae RCV000034406 SCV000252907 benign not provided 2019-01-21 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine,University of Washington RCV000210149 SCV000266139 uncertain significance Colorectal cancer, susceptibility to 2015-11-20 criteria provided, single submitter clinical testing
Color RCV000131447 SCV000681506 likely benign Hereditary cancer-predisposing syndrome 2016-06-24 criteria provided, single submitter clinical testing
Mendelics RCV000198399 SCV000838088 uncertain significance Familial adenomatous polyposis 1 2018-07-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000254627 SCV000918441 uncertain significance not specified 2018-05-11 criteria provided, single submitter clinical testing Variant summary: APC c.2204C>T (p.Ala735Val) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.7e-05 in 275682 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in APC causing Familial Adenomatous Polyposis (4.7e-05 vs 7.1e-05), allowing no conclusion about variant significance. The variant, c.2204C>T, has been reported in the literature in individuals affected with Familial Adenomatous Polyposis, colorectal, breast, and ovarian cancer, but without strong evidence for pathogenicity (Yurgelun_2017 , Yurgelun_2015, Johnston_2012, Kerr_2013, Shirts_2016, Tung_2016) . These report(s) do not provide unequivocal conclusions about association of the variant with Familial Adenomatous Polyposis. Co-occurrences with other pathogenic variant(s) have been reported (APC c.994C>T, p.Arg332X, Kerr_2013; c.5351dupA, p.Asn1784Lysfs*3; Tung_2014), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (uncertain significance x1, likely benign x3, benign x2). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034406 SCV000043113 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
CSER _CC_NCGL, University of Washington RCV000417343 SCV000503559 likely benign Familial adenomatous polyposis 2016-08-01 no assertion criteria provided research Found in patient having exome sequencing due to suspicion for hereditary colon cancer and/or polyps. Patient is a 58 year old with 5-10 colon polyps and a family history of colon cancer.
3DMed Clinical Laboratory Inc RCV000677783 SCV000803939 uncertain significance Neoplasm of the liver 2017-01-09 no assertion criteria provided clinical testing

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