Submissions for variant NM_004360.5(CDH1):c.2296-14T>C

gnomAD frequency: 0.00002  dbSNP: rs755950355

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000581216	SCV000689508	likely benign	Hereditary cancer-predisposing syndrome	2015-11-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000608347	SCV000715344	likely benign	not specified	2017-01-18	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002061794	SCV002429474	likely benign	Hereditary diffuse gastric adenocarcinoma	2023-10-04	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	RCV002061794	SCV003926922	uncertain significance	Hereditary diffuse gastric adenocarcinoma	2022-08-01	criteria provided, single submitter	clinical testing	Not applicable criteria (PMID: 30311375)
Myriad Genetics, Inc.	RCV002061794	SCV005403922	likely benign	Hereditary diffuse gastric adenocarcinoma	2024-09-23	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001358369	SCV001554082	likely benign	not provided		no assertion criteria provided	clinical testing	The CDH1 c.2296-14T>C was not identified in the literature nor was it identified in the dbSNP, Cosmic, MutDB, Insight Colon Cancer Gene Variant, and Zhejiang Colon Cancer databases. The variant was also not identified in the 1000 Genomes and the NHLBI GO Exome Sequencing Projects.The variant was identified in the ClinVar database as likely benign by Color Genomics and GeneDx. The variant was identified in control databases in 5 of 245670 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include Other in 2 of 5476 chromosomes (freq: 0.0004), European Non-Finnish in 3 of 111404 chromosomes (freq: 0.00003), while the variant was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European Finnish, and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. 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 classified as likely benign.