Submissions for variant NM_000038.6(APC):c.8061A>G (p.Ser2687=)

gnomAD frequency: 0.00004  dbSNP: rs746180965

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000424043	SCV000512091	benign	not specified	2015-03-20	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.
Ambry Genetics	RCV000570768	SCV000672513	likely benign	Hereditary cancer-predisposing syndrome	2015-10-15	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Color Diagnostics, LLC DBA Color Health	RCV000570768	SCV000681908	likely benign	Hereditary cancer-predisposing syndrome	2016-07-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586668	SCV000694135	likely benign	not provided	2017-05-22	criteria provided, single submitter	clinical testing	Variant summary: The APC c.8061A>G (p.Ser2687Ser) 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. 3/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 4/121330 control chromosomes, predominantly observed in the Latino subpopulation at a frequency of 0.000259 (3/11574). This frequency is about 4 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 Latino origin. In addition, one other clinical diagnostic laboratory classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely benign.
Invitae	RCV003766194	SCV000768413	likely benign	Familial adenomatous polyposis 1	2024-01-28	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000586668	SCV001470667	likely benign	not provided	2023-08-30	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000424043	SCV004243263	likely benign	not specified	2024-02-06	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003995948	SCV004835758	likely benign	Classic or attenuated familial adenomatous polyposis	2023-12-01	criteria provided, single submitter	clinical testing