Submissions for variant NM_000038.6(APC):c.2262T>G (p.Val754=)

gnomAD frequency: 0.00096  dbSNP: rs148987776

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002228416	SCV000166018	benign	Familial adenomatous polyposis 1	2021-12-17	criteria provided, single submitter	clinical testing
Eurofins NTD LLC (GA)	RCV000152789	SCV000202177	likely benign	not specified	2014-04-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000163307	SCV000213835	likely benign	Hereditary cancer-predisposing syndrome	2014-10-09	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.
Counsyl	RCV000122761	SCV000487788	likely benign	Familial adenomatous polyposis 1	2015-11-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000152789	SCV000512069	benign	not specified	2015-03-27	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.
Color Diagnostics, LLC DBA Color Health	RCV000163307	SCV000681512	benign	Hereditary cancer-predisposing syndrome	2016-03-18	criteria provided, single submitter	clinical testing
PreventionGenetics,PreventionGenetics	RCV000152789	SCV000805378	benign	not specified	2017-01-10	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000758722	SCV000887509	benign	not provided	2017-08-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000152789	SCV000918464	benign	not specified	2017-12-04	criteria provided, single submitter	clinical testing	Variant summary: The APC c.2262T>G (p.Val754Val) variant involves the alteration of a non-conserved nucleotide causing a synonymous change and 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may create ESE binding sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in 102/276142 control chromosomes (gnomAD), predominantly observed in the African subpopulation at a frequency of 0.003833 (92/24002). This frequency is about 54 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), strongly suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign or benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant is classified as benign.
Genetic Services Laboratory,University of Chicago	RCV000152789	SCV002066398	likely benign	not specified	2019-02-14	criteria provided, single submitter	clinical testing
Sema4,Sema4	RCV000163307	SCV002529051	benign	Hereditary cancer-predisposing syndrome	2020-10-01	criteria provided, single submitter	curation