Submissions for variant NM_000038.6(APC):c.4212C>A (p.Ser1404=)

gnomAD frequency: 0.00008  dbSNP: rs144655979

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003764851	SCV000166035	likely benign	Familial adenomatous polyposis 1	2024-01-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000162838	SCV000213325	likely benign	Hereditary cancer-predisposing syndrome	2014-09-25	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Color Diagnostics, LLC DBA Color Health	RCV000162838	SCV000681656	likely benign	Hereditary cancer-predisposing syndrome	2016-06-15	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589752	SCV000694045	benign	not provided	2017-01-03	criteria provided, single submitter	clinical testing	Variant summary: The APC c.4212C>A (p.Ser1404Ser) variant causes a synonymous change involving a non-conserved nucleotide, 4/5 splice prediction tools predict no significant impact on normal splicing and ESE finder predicts alterations to ESE binding, although these predictions have yet to be functionally assessed. The variant of interest has been observed in the large, broad control population, ExAC, with an allele frequency of 11/121300 (1/11025), which exceeds the estimated maximal expected allele frequency for a pathogenic APC variant of 1/14005, therefore, suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Therefore, the variant of interest has been classified as Benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000581831	SCV001470645	benign	not specified	2019-09-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000589752	SCV001830485	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000162838	SCV002531915	likely benign	Hereditary cancer-predisposing syndrome	2020-10-06	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV000589752	SCV004159222	likely benign	not provided	2022-03-01	criteria provided, single submitter	clinical testing	APC: BP4, BP7
Mayo Clinic Laboratories, Mayo Clinic	RCV000581831	SCV000691746	likely benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000589752	SCV001952723	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000589752	SCV001970097	likely benign	not provided		no assertion criteria provided	clinical testing