ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.84C>T (p.Cys28=)

gnomAD frequency: 0.00004  dbSNP: rs587780789
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001079933 SCV000166562 likely benign Hereditary diffuse gastric adenocarcinoma 2024-01-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000163675 SCV000214248 likely benign Hereditary cancer-predisposing syndrome 2014-10-31 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Color Diagnostics, LLC DBA Color Health RCV000163675 SCV000537461 likely benign Hereditary cancer-predisposing syndrome 2015-08-03 criteria provided, single submitter clinical testing
GeneDx RCV000614020 SCV000714356 benign not specified 2015-07-01 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757067 SCV000885156 likely benign not provided 2018-03-28 criteria provided, single submitter clinical testing The CDH1 c.84C>T; p.Cys28Cys variant (rs587780789), to our knowledge, is not reported in the medical literature but is reported as likely benign in ClinVar (Variation ID: 136070). This variant is found in the general population with an overall allele frequency of 0.003% (4/149530 alleles) in the Genome Aggregation Database. This is a synonymous change, the nucleotide is weakly conserved, and computational algorithms do not predict this variant to impact splicing (Alamut v.2.10). Based on available information, this variant is considered to be likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000614020 SCV000919102 likely benign not specified 2018-03-16 criteria provided, single submitter clinical testing Variant summary: CDH1 c.84C>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 allele was found at a frequency of 7.00e-05 within Non-Finnish European control individuals (i.e. 4/57386 control chromosomes) in the gnomAD database, which is approximately 2-fold of the estimated maximal expected allele frequency for a pathogenic variant in CDH1 causing Hereditary Diffuse Gastric Cancer phenotype (2.8e-05), suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.84C>T in individuals affected with Hereditary Diffuse Gastric Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and both of them classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000614020 SCV002551739 likely benign not specified 2023-08-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002505074 SCV002804832 likely benign Familial cancer of breast; Blepharocheilodontic syndrome 1; Endometrial carcinoma; Hereditary diffuse gastric adenocarcinoma; Neoplasm of ovary; Malignant tumor of prostate 2021-12-22 criteria provided, single submitter clinical testing

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.