Submissions for variant NM_004360.5(CDH1):c.688-4T>C

gnomAD frequency: 0.00003  dbSNP: rs781633588

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000218860	SCV000273711	likely benign	Hereditary cancer-predisposing syndrome	2019-05-16	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	RCV000425352	SCV000512509	likely benign	not specified	2017-09-08	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	RCV000218860	SCV000911792	likely benign	Hereditary cancer-predisposing syndrome	2016-04-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000425352	SCV000919096	uncertain significance	not specified	2017-09-19	criteria provided, single submitter	clinical testing	Variant summary: The CDH1 c.688-4T>C variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was found in the control population dataset of gnomAD in 2/246212 control chromosomes at a frequency of 0.0000081, which does not exceed the estimated maximal expected allele frequency of a pathogenic CDH1 variant (0.0000283). The variant has been reported in the literature, without strong evidence for causality (Yorczyk_2015). One clinical diagnostic laboratory classified this variant as uncertain significance and one as likely benign. Taken together, this variant is classified as VUS.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000875193	SCV001017484	likely benign	Hereditary diffuse gastric adenocarcinoma	2023-11-09	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000425352	SCV002070061	likely benign	not specified	2019-12-31	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000875193	SCV005403513	likely benign	Hereditary diffuse gastric adenocarcinoma	2024-09-13	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.