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

gnomAD frequency: 0.00006  dbSNP: rs767053295

Total submissions: 10

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	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.
GeneDx	RCV000589682	SCV000517874	likely benign	not provided	2021-03-28	criteria provided, single submitter	clinical testing
Invitae	RCV003534429	SCV000562585	likely benign	Familial adenomatous polyposis 1	2024-01-16	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163561	SCV000687152	likely benign	Hereditary cancer-predisposing syndrome	2016-11-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000443758	SCV000694128	likely benign	not specified	2019-11-17	criteria provided, single submitter	clinical testing
Counsyl	RCV000459412	SCV000786013	likely benign	Familial adenomatous polyposis 1	2018-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000589682	SCV000805473	likely benign	not provided	2017-11-10	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000589682	SCV001471958	likely benign	not provided	2020-06-09	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000459412	SCV004018712	benign	Familial adenomatous polyposis 1	2023-02-17	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000589682	SCV000591053	likely benign	not provided		no assertion criteria provided	clinical testing	The p.Gly263Gly 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. The variant was identified in the ClinVar database (classified as “likely benign” by Ambry Genetics), and in the Exome Aggregation Consortium (ExAC) database where it was present at a very low frequency in a population of European individuals (4/66322 chromosomes, or frequency of 0.00006). The variant was not identified in the literature, nor was it identified in any of the following databases: dbSNP, NHLBI Exome Sequencing Project (Exome Variant Server), COSMIC, InSiGHT Colon Cancer Gene Variant Database, “Zhejiang Colon Cancer Database”, GeneInsight COGR database, and UMD. In silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict the creation of a cryptic splice site. 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 predicted benign.