Submissions for variant NM_004360.5(CDH1):c.2387G>A (p.Arg796Gln)

gnomAD frequency: 0.00004  dbSNP: rs587782549

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000131762	SCV000186806	likely benign	Hereditary cancer-predisposing syndrome	2018-05-03	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.
GeneDx	RCV000587217	SCV000278917	uncertain significance	not provided	2023-09-06	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28202063, 29295527, 15235021, 22850631, 32283892, 31159747)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000228473	SCV000288465	likely benign	Hereditary diffuse gastric adenocarcinoma	2024-01-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002271418	SCV000698383	likely benign	not specified	2023-10-02	criteria provided, single submitter	clinical testing	Variant summary: CDH1 c.2387G>A (p.Arg796Gln) results in a conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.7e-05 in 403358 control chromosomes. The observed variant frequency is slightly higher than the estimated maximal expected allele frequency for a pathogenic variant in CDH1 causing Hereditary Diffuse Gastric Cancer phenotype (2.8e-05), suggesting that the variant is benign. A recent case-control study showed that this variant was not associated with breast cancer (Dorling_2021). The following publication has been ascertained in the context of this evaluation (PMID: 33471991). Nine submitters have submitted clinical-significance assessments for this variant to ClinVar after 2014; they reported the variant with conflicting assessments (Likely Benign n=3, VUS n=6). Based on the evidence outlined above, the variant was classified as likely benign.
GeneKor MSA	RCV000131762	SCV000821973	uncertain significance	Hereditary cancer-predisposing syndrome	2018-08-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000131762	SCV000903152	likely benign	Hereditary cancer-predisposing syndrome	2021-03-18	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000587217	SCV001134078	uncertain significance	not provided	2019-03-22	criteria provided, single submitter	clinical testing
Mendelics	RCV000228473	SCV001140152	uncertain significance	Hereditary diffuse gastric adenocarcinoma	2019-05-28	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000587217	SCV002009855	uncertain significance	not provided	2021-11-03	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	RCV000228473	SCV003926934	uncertain significance	Hereditary diffuse gastric adenocarcinoma	2022-08-01	criteria provided, single submitter	clinical testing	BS2_Supporting (PMID: 30311375)
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002271418	SCV004242735	uncertain significance	not specified	2024-02-06	criteria provided, single submitter	clinical testing