Submissions for variant NM_004360.5(CDH1):c.163+4_163+6dup

dbSNP: rs1205684749

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen CDH1 Variant Curation Expert Panel	RCV003328257	SCV001437620	likely benign	CDH1-related diffuse gastric and lobular breast cancer syndrome	2023-08-17	reviewed by expert panel	curation	The CDH1 c.163+4_163+6dupAGG variant occurs in the splice donor region of intron 2. This allele is present at a frequency of 0.00001338 (2 in 149,510 alleles) in the gnomAD database (GRCh37) (http://gnomad.broadinstitute.org). This variant has been observed in more than ten individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2; SCV000969083.1, SCV000216473.4, SCV000637738.2). In summary, this variant is classified as likely benign based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2.
Ambry Genetics	RCV000165732	SCV000216473	likely benign	Hereditary cancer-predisposing syndrome	2023-11-03	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.
Counsyl	RCV000408987	SCV000488939	likely benign	Hereditary diffuse gastric adenocarcinoma	2016-07-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000408987	SCV000637738	likely benign	Hereditary diffuse gastric adenocarcinoma	2023-12-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000827437	SCV000969083	likely benign	not provided	2021-05-05	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002465552	SCV002760847	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000408987	SCV004019534	likely benign	Hereditary diffuse gastric adenocarcinoma	2023-03-03	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	RCV000827437	SCV004220797	likely benign	not provided	2023-06-06	criteria provided, single submitter	clinical testing