Submissions for variant NM_000038.6(APC):c.1713A>G (p.Ala571=)

gnomAD frequency: 0.00002  dbSNP: rs529306174

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000424947	SCV000512065	benign	not specified	2015-03-19	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	RCV000551505	SCV000647194	likely benign	Familial adenomatous polyposis 1	2024-01-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000568491	SCV000667231	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: 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	RCV000568491	SCV000681486	likely benign	Hereditary cancer-predisposing syndrome	2016-11-15	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001284234	SCV001469901	likely benign	not provided	2022-11-11	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000551505	SCV000591086	likely benign	Familial adenomatous polyposis 1		no assertion criteria provided	clinical testing	The APC p.Ala571Ala 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, HumanSpliceFinder) do not predict a difference in splicing. The variant was not identified in the literature, nor was it identified in dbSNP, the NHLBI Exome Sequencing Project (Exome Variant Server), HGMD, UMD, the “InSiGHT Colon Cancer Database”, or the COSMIC database. This variant was identified by our laboratory in a patient with a co-occurring pathogenic MUTYH mutation in homozygous state, increasing the likelihood that the APC p.Ala571Ala variant does not have clinical significance. 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 predicted benign.