Submissions for variant NM_000038.6(APC):c.7490C>T (p.Ser2497Leu)

gnomAD frequency: 0.00031  dbSNP: rs141010008

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV004562271	SCV000166057	benign	Familial adenomatous polyposis 1	2025-02-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000131590	SCV000186602	benign	Hereditary cancer-predisposing syndrome	2015-09-12	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
GeneDx	RCV000587624	SCV000209549	likely benign	not provided	2020-08-25	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24728327, 25801821, 23910461, 11818965, 28389531)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587624	SCV000694118	benign	not provided	2016-03-25	criteria provided, single submitter	clinical testing	Variant Summary: The c.7490C>T variant involves the alteration of a conserved nucleotide and 3/4 in silico tools predict a neutral outcome. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.033%, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.055%. This frequency exceeds the maximal expected allele frequency for a pathogenic variant in APC (0.006%), suggesting this is a benign polymorphism found primarily in population(s) of European origin. The variant was reported in a family affected by multiple colorectal adenomas and carcinoma, however was absent in two affected members and was present in 3 unaffected members, showing lack of segregation of the variant with disease (Al-Tassan_2002). While one reputable clinical lab has classified the variant as likely benign, others have classified it as a VUS. Considering the relatively high frequency of this variant in the general population as well as the lack of segregation seen in an affected family, this variant has been classified as Benign.
Mendelics	RCV004562271	SCV000838150	benign	Familial adenomatous polyposis 1	2023-08-22	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000131590	SCV000910611	benign	Hereditary cancer-predisposing syndrome	2016-03-22	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000587624	SCV001133368	likely benign	not provided	2020-02-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000587624	SCV001154481	uncertain significance	not provided	2022-01-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001153055	SCV001314303	likely benign	APC-Associated Polyposis Disorders	2019-02-19	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000587624	SCV002011084	likely benign	not provided	2021-11-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587624	SCV002049735	likely benign	not provided	2021-04-06	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000120032	SCV002069711	likely benign	not specified	2021-04-30	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000131590	SCV002528093	benign	Hereditary cancer-predisposing syndrome	2020-06-10	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000120032	SCV002550657	likely benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004562271	SCV005083665	likely benign	Familial adenomatous polyposis 1	2024-04-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].
ITMI	RCV000120032	SCV000084163	not provided	not specified	2013-09-19	no assertion provided	reference population
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000587624	SCV001744322	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000587624	SCV001920215	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000587624	SCV001952102	likely benign	not provided		no assertion criteria provided	clinical testing