Submissions for variant NM_000038.6(APC):c.7869A>G (p.Thr2623=)

dbSNP: rs775126492

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000776837	SCV000912496	likely benign	Hereditary cancer-predisposing syndrome	2017-11-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000776837	SCV001189362	likely benign	Hereditary cancer-predisposing syndrome	2018-08-24	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.
Invitae	RCV003653315	SCV001653996	likely benign	Familial adenomatous polyposis 1	2023-12-27	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003478472	SCV004220618	uncertain significance	not provided	2022-10-18	criteria provided, single submitter	clinical testing	To the best of our knowledge, the variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant does not affect APC mRNA splicing. Based on the available information, we are unable to determine the clinical significance of this variant.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354138	SCV001548680	uncertain significance	Carcinoma of colon		no assertion criteria provided	clinical testing	The APC p.Thr2623= variant was not identified in the literature nor was it identified in the dbSNP, LOVD 3.0, or UMD-LSDB, databases. The variant was only identified in ClinVar (classified as likely benign by Color). The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Thr2623= 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. The variant occurs outside of the splicing consensus sequence and 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.