ClinVar Miner

Submissions for variant NM_000038.6(APC):c.789T>A (p.Gly263=) (rs767053295)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163561 SCV000214119 likely benign Hereditary cancer-predisposing syndrome 2014-09-17 criteria provided, single submitter clinical testing
GeneDx RCV000443758 SCV000517874 likely benign not specified 2017-08-03 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 RCV000459412 SCV000562585 likely benign Familial adenomatous polyposis 1 2017-12-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000443758 SCV000591053 likely benign not specified 2015-07-28 criteria provided, single submitter clinical testing
Color RCV000163561 SCV000687152 likely benign Hereditary cancer-predisposing syndrome 2016-11-22 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000443758 SCV000694128 likely benign not specified 2018-08-17 criteria provided, single submitter clinical testing Variant summary: APC c.789T>A alters a non-conserved nucleotide resulting in a synonymous change. Three of five computational tools predict the variant to disrupt a 5' cryptic donor splice site which would be expected to enhance rather than abolish normal splicing. However, these predictions have yet to be tested in experimental systems. The variant allele was found at a frequency of 5.1e-05 in 276868 control chromosomes in gnomAD, but was predominantly found in the Non-Finnish European subpopulation at a frequency of 0.0001 (13/126532 chromosomes). This frequency is ~1.5x higher than expected for a pathogenic variant in APC causing Familial Adenomatous Polyposis (5.1e-05 vs 7.1e-05), suggesting the variant may be a benign polymorphism found in Non-Finnish European populations. To our knowledge, no occurrence of c.789T>A in individuals affected with Familial Adenomatous Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Counsyl RCV000459412 SCV000786013 likely benign Familial adenomatous polyposis 1 2018-02-01 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000589682 SCV000805473 likely benign not provided 2017-11-10 criteria provided, single submitter clinical testing

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