Submissions for variant NM_000038.6(APC):c.6135C>T (p.Ser2045=)

gnomAD frequency: 0.00004  dbSNP: rs187297940

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV004567056	SCV000166047	likely benign	Familial adenomatous polyposis 1	2024-01-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000435748	SCV000512081	benign	not specified	2015-05-14	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	RCV000574161	SCV000667295	likely benign	Hereditary cancer-predisposing syndrome	2015-04-28	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	RCV000574161	SCV000681784	likely benign	Hereditary cancer-predisposing syndrome	2016-12-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000679075	SCV000805447	likely benign	not provided	2018-01-25	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000679075	SCV002497340	likely benign	not provided	2022-03-01	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000574161	SCV002536383	likely benign	Hereditary cancer-predisposing syndrome	2021-04-29	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000435748	SCV002550638	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000679075	SCV004219634	likely benign	not provided	2023-03-08	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003997382	SCV004838149	likely benign	Classic or attenuated familial adenomatous polyposis	2024-01-11	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004567056	SCV005084503	benign	Familial adenomatous polyposis 1	2024-04-03	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	RCV001353604	SCV000591196	likely benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The APC p.Ser2045Ser variant was not identified in the literature. The variant was identified in dbSNP (ID: rs 187297940) “With likely benign allele”, Clinvitae database (as likely benign), ClinVar database (classified as “likely benign” by Invitae) and the Exome Aggregation Consortium (ExAC) database (released Jan 13, 2015) in 8 of 66680 chromosomes (frequency: 0.00012) from a population of European (Non-Finnish) individuals as well as at extremely low frequencies in European (Finnish) (0.00015) and South Asian (0.00006) populations, although this low number of observations and low frequency is not substantive enough to determine the prevalence of the variant in the general population and its relationship to disease. The p.Ser2045Ser 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. 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 likely benign.