Submissions for variant NM_000038.6(APC):c.1458T>C (p.Tyr486=)

gnomAD frequency: 0.46792  dbSNP: rs2229992

Total submissions: 23

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel	RCV003148640	SCV003836582	benign	Familial adenomatous polyposis 1	2023-02-19	reviewed by expert panel	curation	The c.1458T>C (p.Tyr486=) variant in APC is a synonymous (silent) variant that is not predicted to impact splicing (BP4, BP7). The highest population minor allele frequency (non-cancer) in gnomAD v2.1.1 is 69.75% in Latino/Admixed American population, which is higher than the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (HCCP VCEP) threshold (0.1%) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as Benign for FAP based on the ACMG/AMP criteria applied, as specified by the HCCP VCEP: BA1, BP4, BP7 (VCEP specifications Version 1.0, date of approval: 12/12/2022).
Eurofins Ntd Llc (ga)	RCV000035064	SCV000109810	benign	not specified	2016-03-16	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000131423	SCV000186404	benign	Hereditary cancer-predisposing syndrome	2014-10-24	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.
PreventionGenetics, part of Exact Sciences	RCV000035064	SCV000301587	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000275522	SCV000451988	benign	APC-Associated Polyposis Disorders	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001675589	SCV000602510	benign	not provided	2024-11-27	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003148640	SCV000647179	benign	Familial adenomatous polyposis 1	2025-02-04	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000131423	SCV000681463	benign	Hereditary cancer-predisposing syndrome	2016-03-18	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000755636	SCV000883033	benign	Desmoid disease, hereditary; Carcinoma of colon; Familial adenomatous polyposis 1; Neoplasm of stomach; Hepatocellular carcinoma	2018-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001675589	SCV001894230	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30272267)
Pathology and Clinical Laboratory Medicine, King Fahad Medical City	RCV000035064	SCV002073833	benign	not specified		criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000131423	SCV002535674	benign	Hereditary cancer-predisposing syndrome	2019-12-09	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003148640	SCV004017494	benign	Familial adenomatous polyposis 1	2023-07-07	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035064	SCV000058704	benign	not specified	2008-03-01	no assertion criteria provided	clinical testing
Systems Biology Platform Zhejiang California International NanoSystems Institute	RCV000074147	SCV000105740	cancer	Familial colorectal cancer		no assertion criteria provided	not provided	Converted during submission to other.
Mayo Clinic Laboratories, Mayo Clinic	RCV000035064	SCV000256922	benign	not specified		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353619	SCV000591074	benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The c.1458T>C, p.Tyr486Tyr silent variant, located in exon 12 of APC, is not expected to have clinical significance because it does not alter an amino acid residue, is not located near a splice junction, is listed in dbSNP (rs_id:rs2229992) with a minor allele frequency of 0.46. Based on the above information, this is a likely benign variant.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000035064	SCV001744287	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035064	SCV001918098	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035064	SCV001957590	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000035064	SCV001970515	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000035064	SCV001977893	benign	not specified		no assertion criteria provided	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000131423	SCV002050299	benign	Hereditary cancer-predisposing syndrome	2021-12-21	no assertion criteria provided	clinical testing