Submissions for variant NM_000038.6(APC):c.6945A>G (p.Gln2315=)

gnomAD frequency: 0.00003  dbSNP: rs786201348

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163446	SCV000213993	likely benign	Hereditary cancer-predisposing syndrome	2015-05-11	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.
Counsyl	RCV000410447	SCV000488797	likely benign	Familial adenomatous polyposis 1	2016-06-23	criteria provided, single submitter	clinical testing
GeneDx	RCV001721044	SCV000512083	likely benign	not provided	2019-10-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000410447	SCV000562635	likely benign	Familial adenomatous polyposis 1	2024-11-05	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163446	SCV000911742	likely benign	Hereditary cancer-predisposing syndrome	2017-12-14	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163446	SCV002526886	likely benign	Hereditary cancer-predisposing syndrome	2021-09-11	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000410447	SCV004018734	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.
All of Us Research Program, National Institutes of Health	RCV003995255	SCV004843479	likely benign	Classic or attenuated familial adenomatous polyposis	2023-12-01	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000410447	SCV001549763	likely benign	Familial adenomatous polyposis 1		no assertion criteria provided	clinical testing	The APC p.Gln2315= variant was not identified in the literature nor was it identified in the LOVD 3.0 or UMD-LSDB databases. The variant was identified in dbSNP (ID: rs786201348) as "With Likely benign allele”, ClinVar (classified as likely benign by Invitae, Ambry Genetics and three other submitters). The variant was identified in control databases in 3 of 276668 chromosomes at a frequency of 0.00001 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the European population in 3 of 126290 chromosomes (freq: 0.00002), while it was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Gln2315= 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 addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. 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.
PreventionGenetics, part of Exact Sciences	RCV003907504	SCV004724680	likely benign	APC-related disorder	2019-08-13	no assertion criteria provided	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).