Submissions for variant NM_004360.5(CDH1):c.2412C>T (p.Pro804=)

gnomAD frequency: 0.00018  dbSNP: rs202075199

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000162624	SCV000213059	likely benign	Hereditary cancer-predisposing syndrome	2014-08-29	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	RCV001086470	SCV000253420	likely benign	Hereditary diffuse gastric adenocarcinoma	2025-02-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000435172	SCV000512530	benign	not specified	2015-08-04	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.
Color Diagnostics, LLC DBA Color Health	RCV000162624	SCV000537459	likely benign	Hereditary cancer-predisposing syndrome	2015-07-20	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757066	SCV000885155	likely benign	not provided	2018-02-07	criteria provided, single submitter	clinical testing	The CDH1 c.2412C>T; p.Pro804Pro variant (rs202075199), to our knowledge, is not reported in the medical literature but is classified as benign or likely benign in ClinVar (Variation ID: 183811). This variant is found in the general population with an overall allele frequency of 0.008% (21/277046 alleles) in the Genome Aggregation Database. This is a synonymous change, the nucleotide is not conserved, and computational algorithms do not predict this variant to impact splicing (Alamut v.2.10). Based on available information, this variant is considered likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000757066	SCV000889250	benign	not provided	2022-08-04	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000757066	SCV002497926	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	CDH1: BP4, BP7
Sema4, Sema4	RCV000162624	SCV002529132	benign	Hereditary cancer-predisposing syndrome	2021-02-05	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000435172	SCV002551795	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000162624	SCV002819154	benign	Hereditary cancer-predisposing syndrome	2022-12-23	criteria provided, single submitter	clinical testing
European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto	RCV001086470	SCV003926938	uncertain significance	Hereditary diffuse gastric adenocarcinoma	2022-08-01	criteria provided, single submitter	clinical testing	BP7 (PMID: 30311375)
Myriad Genetics, Inc.	RCV001086470	SCV005405277	benign	Hereditary diffuse gastric adenocarcinoma	2024-09-23	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.
PreventionGenetics, part of Exact Sciences	RCV003952806	SCV004773984	likely benign	CDH1-related disorder	2019-04-09	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).