Submissions for variant NM_000038.6(APC):c.8261G>A (p.Ser2754Asn)

gnomAD frequency: 0.00004  dbSNP: rs369721828

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000590250	SCV000149037	likely benign	not provided	2020-12-02	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27978560, 25203624)
Ambry Genetics	RCV000115128	SCV000185823	benign	Hereditary cancer-predisposing syndrome	2015-08-03	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000197863	SCV000254046	likely benign	Familial adenomatous polyposis 1	2024-01-27	criteria provided, single submitter	clinical testing
Counsyl	RCV000197863	SCV000488248	uncertain significance	Familial adenomatous polyposis 1	2016-02-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000722129	SCV000694140	likely benign	not specified	2017-11-24	criteria provided, single submitter	clinical testing	Variant summary: The APC c.8261G>A (p.Ser2754Asn) variant located in the EB-1 binding domain (InterPro) involves the alteration of a non-conserved nucleotide and 4/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). However, these predictions have yet to be functionally assessed. This variant was found in 21/276830 control chromosomes, predominantly observed in the Ashkenazi Jewish subpopulation at a frequency of 0.001579 (16/10136). This frequency is about 22 times the estimated maximal expected allele frequency of a pathogenic APC variant (0.0000714), suggesting this is likely a benign polymorphism found primarily in Ashkenazi Jewish individuals. A publication, Pearlman_2017, cites the variant in a female diagnosed with colorectal cancer, however, limited information is provided (ie, lack of cosegregation data). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as "uncertain significance" or "benign." Taken together, this variant is classified as likely benign.
Color Diagnostics, LLC DBA Color Health	RCV000115128	SCV000910685	likely benign	Hereditary cancer-predisposing syndrome	2016-03-23	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000590250	SCV002046440	benign	not provided	2020-11-20	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000115128	SCV002531659	likely benign	Hereditary cancer-predisposing syndrome	2021-06-13	criteria provided, single submitter	curation
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000115128	SCV004014977	uncertain significance	Hereditary cancer-predisposing syndrome	2023-05-03	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000197863	SCV004018792	uncertain significance	Familial adenomatous polyposis 1	2023-02-22	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000722129	SCV004025087	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000590250	SCV004185295	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	APC: BP4
All of Us Research Program, National Institutes of Health	RCV003997232	SCV004835787	likely benign	Classic or attenuated familial adenomatous polyposis	2024-02-05	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003952546	SCV004775959	likely benign	APC-related disorder	2020-01-13	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).