Submissions for variant NM_000038.6(APC):c.5265G>A (p.Ala1755=)

gnomAD frequency: 0.00675  dbSNP: rs34506289

Total submissions: 25

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV004562225	SCV000153871	benign	Familial adenomatous polyposis 1	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000035075	SCV000167013	benign	not specified	2013-10-10	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.
Ambry Genetics	RCV000128954	SCV000172833	benign	Hereditary cancer-predisposing syndrome	2014-11-24	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.
Eurofins Ntd Llc (ga)	RCV000035075	SCV000226387	benign	not specified	2014-12-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000035075	SCV000301598	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000298427	SCV000452023	benign	APC-Associated Polyposis Disorders	2018-01-12	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	RCV000513120	SCV000602517	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000513120	SCV000609171	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	APC: BP4, BP7, BS1, BS2
Color Diagnostics, LLC DBA Color Health	RCV000128954	SCV000681721	benign	Hereditary cancer-predisposing syndrome	2016-03-17	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000513120	SCV002010873	likely benign	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000035075	SCV002069709	benign	not specified	2018-08-01	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000128954	SCV002535131	benign	Hereditary cancer-predisposing syndrome	2020-07-28	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000035075	SCV002550631	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000128954	SCV004015001	benign	Hereditary cancer-predisposing syndrome	2023-06-02	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004562225	SCV005084438	benign	Familial adenomatous polyposis 1	2024-04-01	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.
Breakthrough Genomics, Breakthrough Genomics	RCV000513120	SCV005219861	likely benign	not provided		criteria provided, single submitter	not provided
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035075	SCV000058715	benign	not specified	2008-03-01	no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000128954	SCV000693484	likely benign	Hereditary cancer-predisposing syndrome	2017-08-11	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000035075	SCV001551696	benign	not specified		no assertion criteria provided	clinical testing	The APC p.Ala1755Ala variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located near a splice junction, and is listed in dbSNP (rs34506289) with a minor allele frequency (MAF) score of 0.004, having been observed in 9/2250 chromosomes (1000 Genomes). It was reported in 3/132 proband chromosomes of individuals with multiple colorectal adenomas and carcinomas, familial adenomatous polyposis (FAP) and sporadic polyposis, and also observed in 2/100 control chromosomes evaluated (Al-Tassan 2002, Hadjisavvas 2006, Kanter-Smoler 2006). In the latter study, the variant was found in the proband and his healthy sister along with the FAP-modifying polymorphism p.E1317Q, while his disease-affected brother did not harbour either variants (Kanter-Smoler 2006). These observations increase the likelihood that the variant is of little or no clinical significance. The variant was also reported in the Exome Variant Server and LOVD databases. This variant is classified as benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000035075	SCV001799393	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000035075	SCV001809345	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000035075	SCV001905963	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035075	SCV001918973	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000513120	SCV001955887	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000035075	SCV001965610	benign	not specified		no assertion criteria provided	clinical testing