ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.387+6T>C

gnomAD frequency: 0.00001  dbSNP: rs764434962
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel RCV003328337 SCV001943362 likely benign CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-17 reviewed by expert panel curation c.387+6T>C is an intronic variant in the splice donor region of intron 3. This variant has an allele frequency of 0.0001 (5/34548 alleles) in the gnomAD v2.1 Latino/admixed American sub-population (http://gnomad.broadinstitute.org). This variant has been reported in at least 13 individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2; SCV000637825.4). This variant is predicted to have no impact on splicing by multiple in silico splice site predictors (BP4; SpliceAI, varSEAK, MaxEntScan). In summary, this variant meets criteria to be 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, BP4.
GeneDx RCV000589852 SCV000529222 likely benign not provided 2018-06-12 criteria provided, single submitter clinical testing
Invitae RCV000539158 SCV000637825 likely benign Hereditary diffuse gastric adenocarcinoma 2023-09-17 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589852 SCV000698399 uncertain significance not provided 2016-09-26 criteria provided, single submitter clinical testing Variant summary: The CDH1 c.387+6T>C variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESEfinder predicts a gain of binding motif for splicing enhancer SC15. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1/119366 control chromosomes, predominantly observed in the Latino subpopulation at a frequency of 0.000088 (1/11358). This frequency is about 3 times the estimated maximal expected allele frequency of a pathogenic CDH1 variant (0.0000283), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS)-possibly benign until additional information becomes available.
Color Diagnostics, LLC DBA Color Health RCV000776451 SCV000911983 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-09 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589852 SCV004220831 likely benign not provided 2023-03-10 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.