Submissions for variant NM_000038.6(APC):c.6921G>A (p.Ser2307=)

gnomAD frequency: 0.00143  dbSNP: rs2229993

Total submissions: 23

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000211932	SCV000167014	benign	not specified	2014-01-06	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	RCV000128942	SCV000172817	benign	Hereditary cancer-predisposing syndrome	2014-12-13	criteria provided, single submitter	clinical testing	This alteration is classified as 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	RCV003534366	SCV000252592	benign	Familial adenomatous polyposis 1	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000398735	SCV000452042	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.
Genetic Services Laboratory, University of Chicago	RCV000211932	SCV000593258	likely benign	not specified	2017-04-27	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000128942	SCV000681834	benign	Hereditary cancer-predisposing syndrome	2016-03-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586387	SCV000694103	benign	not provided	2016-02-23	criteria provided, single submitter	clinical testing	Variant summary: The APC c.6921G>A variant affects a non-conserved nucleotide, resulting in a synonymous change at Ser2307. 5/5 Alamut algorithms predict no significant change to normal splicing. ESEfinder predicts a loss of binding motif for RNA splicing enhancer. These in silico predictions have not been verified with in vitro/in vivo functional studies. This variant was found in 169/120898 control chromosomes at a frequency of 0.0013979, which is about 23 times the maximal expected frequency of a pathogenic APC allele (0.0000602), suggesting this variant is benign. In addition, multiple clinical laboratories database classified this variant as benign. Taken together, this variant was classified as benign.
PreventionGenetics, part of Exact Sciences	RCV000211932	SCV000805459	benign	not specified	2017-03-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000586387	SCV001154479	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	APC: BP4, BP7, BS1
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000211932	SCV001156604	benign	not specified	2019-01-30	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000586387	SCV002010862	likely benign	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000128942	SCV002526853	benign	Hereditary cancer-predisposing syndrome	2020-10-18	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000211932	SCV002550650	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000128942	SCV004014973	benign	Hereditary cancer-predisposing syndrome	2023-04-18	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353599	SCV000591205	likely benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The APC, c.6921G>A, p.Ser2307Ser variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located near a splice junction. It is listed in dbSNP database (ID#: rs2229993) with a global minor allele frequency (MAF) of 0.001/3. It has been reported in the InSiGHT colon cancer database as a rare familial variant found in a proband with an attenuated colorectal phenotype and sebaceous cysts. The number of probands with the variant, was not provided. In addition, this variant is not of the type that is expected to cause the disorder. In summary, we cannot rule out the possibility that this variant may contribute to the phenotype in this individual, but based on the above information this variant is classified as predicted benign.
Mayo Clinic Laboratories, Mayo Clinic	RCV000211932	SCV000691761	likely benign	not specified		no assertion criteria provided	clinical testing
True Health Diagnostics	RCV000128942	SCV000693487	likely benign	Hereditary cancer-predisposing syndrome	2017-09-11	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000586387	SCV001743076	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000211932	SCV001797927	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000211932	SCV001806794	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000586387	SCV001919592	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000211932	SCV001960064	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000586387	SCV001970882	likely benign	not provided		no assertion criteria provided	clinical testing