ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2331C>T (p.Asp777=)

gnomAD frequency: 0.00003  dbSNP: rs114265540
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163215 SCV000213738 likely benign Hereditary cancer-predisposing syndrome 2014-12-10 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.
Invitae RCV001083083 SCV000288460 likely benign Hereditary diffuse gastric adenocarcinoma 2024-01-16 criteria provided, single submitter clinical testing
GeneDx RCV000759728 SCV000515835 likely benign not provided 2019-08-14 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 27284491)
Color Diagnostics, LLC DBA Color Health RCV000163215 SCV000684424 likely benign Hereditary cancer-predisposing syndrome 2016-12-12 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000434954 SCV000889249 benign not specified 2018-03-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000434954 SCV000919106 benign not specified 2018-04-30 criteria provided, single submitter clinical testing Variant summary: CDH1 c.2331C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was observed with an allele frequency of 6.1e-05 in 246240 control chromosomes (gnomAD). The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 8-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in CDH1 causing Hereditary Diffuse Gastric Cancer phenotype (2.8e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. The variant, c.2331C>T, has been reported in the literature as a somatic occurrence in an individual (Wheeler_2016). This report does not provide unequivocal conclusions about association of the variant with Hereditary Diffuse Gastric Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely benign." Based on the evidence outlined above, the variant was classified as benign.
Illumina Laboratory Services, Illumina RCV001083083 SCV001274532 likely benign Hereditary diffuse gastric adenocarcinoma 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Sema4, Sema4 RCV000163215 SCV002529126 likely benign Hereditary cancer-predisposing syndrome 2021-02-05 criteria provided, single submitter curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000434954 SCV004026656 likely benign not specified 2023-08-15 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003945266 SCV004762483 likely benign CDH1-related disorder 2019-11-15 criteria provided, single submitter 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).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.