Submissions for variant NM_000038.6(APC):c.2232T>G (p.Ser744=)

gnomAD frequency: 0.00032  dbSNP: rs145751759

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163199	SCV000213721	likely benign	Hereditary cancer-predisposing syndrome	2014-09-24	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	RCV000439758	SCV000512068	benign	not specified	2015-07-02	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	RCV000462393	SCV000562574	benign	Familial adenomatous polyposis 1	2024-02-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000439758	SCV000602520	likely benign	not specified	2016-10-18	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163199	SCV000681509	likely benign	Hereditary cancer-predisposing syndrome	2016-03-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590422	SCV000694011	benign	not provided	2016-07-01	criteria provided, single submitter	clinical testing	Variant summary: The APC c.2232T>G (p.Ser744Ser) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant, and 1/5 splicing algorithms predict the loss of a cryptic splicing acceptor site. The variant of interest has not, to our knowledge, been evaluated for functional impact by in vivo/vitro studies. This variant was found in 10/120424 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0009762 (10/10244). This frequency is about 14 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, one clinical diagnostic laboratory classified this variant as likely benign. Taken together, this variant is classified as Benign.
Counsyl	RCV000462393	SCV000785981	likely benign	Familial adenomatous polyposis 1	2018-01-29	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000590422	SCV000861179	uncertain significance	not provided	2018-05-25	criteria provided, single submitter	clinical testing
Mendelics	RCV000462393	SCV001136890	likely benign	Familial adenomatous polyposis 1	2019-05-28	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163199	SCV002536650	benign	Hereditary cancer-predisposing syndrome	2020-10-27	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000439758	SCV002774445	benign	not specified	2021-08-25	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000462393	SCV004018698	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.
PreventionGenetics, part of Exact Sciences	RCV003917561	SCV004742261	likely benign	APC-related condition	2019-09-25	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).