Submissions for variant NM_004360.5(CDH1):c.1566-7C>T

gnomAD frequency: 0.00001  dbSNP: rs747783435

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000227529	SCV000288439	likely benign	Hereditary diffuse gastric adenocarcinoma	2023-12-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000423149	SCV000512523	likely benign	not specified	2016-01-06	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	RCV000580347	SCV000684364	likely benign	Hereditary cancer-predisposing syndrome	2016-12-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000423149	SCV000917118	uncertain significance	not specified	2017-09-28	criteria provided, single submitter	clinical testing	Variant summary: The CDH1 c.1566-7C>T variant involves the alteration of a non-conserved intronic nucleotide and 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 2/246246 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). Multiple clinical diagnostic laboratoriesclassified this variant as likely benign without additional information to allow for an independent evaluation. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.
Myriad Genetics, Inc.	RCV000227529	SCV005404530	likely benign	Hereditary diffuse gastric adenocarcinoma	2024-09-19	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing.
PreventionGenetics, part of Exact Sciences	RCV004739631	SCV005351007	likely benign	CDH1-related disorder	2019-06-20	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).