Submissions for variant NM_000038.6(APC):c.2322C>T (p.Asp774=)

gnomAD frequency: 0.00041  dbSNP: rs145792879

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000211902	SCV000167001	benign	not specified	2014-01-27	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	RCV000123662	SCV000213071	likely benign	Hereditary cancer-predisposing syndrome	2014-08-22	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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	RCV000197095	SCV000252580	benign	Familial adenomatous polyposis 1	2025-02-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000211902	SCV000301591	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000378186	SCV000451996	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Counsyl	RCV000197095	SCV000487922	likely benign	Familial adenomatous polyposis 1	2015-12-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000123662	SCV000681517	likely benign	Hereditary cancer-predisposing syndrome	2016-09-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001528737	SCV002497338	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	APC: BP4, BP7
Sema4, Sema4	RCV000123662	SCV002535398	benign	Hereditary cancer-predisposing syndrome	2020-11-06	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000211902	SCV002550599	likely benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000197095	SCV004018755	benign	Familial adenomatous polyposis 1	2023-02-21	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.
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000123662	SCV004227992	benign	Hereditary cancer-predisposing syndrome	2023-07-27	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001528737	SCV005876717	likely benign	not provided	2024-03-13	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353855	SCV000591110	benign	Carcinoma of colon		no assertion criteria provided	clinical testing	APC, Exon 18, c.2322C>T, p.Asp774Asp, Heterozygous, Predicted Benign. The p.Asp774Asp is not expected to have clinical significance because it does not alter an amino acid residue and is not located near a splice junction. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time, although we would lean towards a more benign role for this variant. This variant is predicted benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528737	SCV001740979	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001528737	SCV001798561	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001528737	SCV001808258	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001528737	SCV001918131	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001528737	SCV001955302	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528737	SCV001973583	likely benign	not provided		no assertion criteria provided	clinical testing