Submissions for variant NM_004360.5(CDH1):c.1137+9A>G

dbSNP: rs780705655

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000456880	SCV000545468	likely benign	Hereditary diffuse gastric adenocarcinoma	2023-10-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000609431	SCV000723781	likely benign	not specified	2017-10-13	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	RCV000774766	SCV000908731	uncertain significance	Hereditary cancer-predisposing syndrome	2024-01-17	criteria provided, single submitter	clinical testing	This variant causes an A to G nucleotide substitution at the +9 position of intron 8 of the CDH1 gene. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with an unspecified cancer that was not diffuse gastric or lobular breast cancer (PMID: 36436516). This variant has been identified in 3/251452 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto	RCV000456880	SCV003926735	uncertain significance	Hereditary diffuse gastric adenocarcinoma	2022-08-01	criteria provided, single submitter	clinical testing	Not applicable criteria (PMID: 30311375)
Ambry Genetics	RCV000774766	SCV004848950	uncertain significance	Hereditary cancer-predisposing syndrome	2015-03-13	criteria provided, single submitter	clinical testing	The c.1137+9A>G intronic alteration consists of a A to G substitution nucleotides after coding exon 8 in the CDH1 gene. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Myriad Genetics, Inc.	RCV000456880	SCV005407636	likely benign	Hereditary diffuse gastric adenocarcinoma	2024-09-18	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV004999439	SCV005624925	uncertain significance	not provided	2024-08-20	criteria provided, single submitter	clinical testing	The CDH1 c.1137+9A>G variant has been reported in the published literature in an individual with a personal history of cancer (PMID: 36436516 (2023)). The frequency of this variant in the general population, 0.000012 (3/251452 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant does not affect CDH1 mRNA splicing. Based on the available information, we are unable to determine the clinical significance of this variant.