ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.49-8C>A

gnomAD frequency: 0.00001  dbSNP: rs774761552
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000421124 SCV000528085 likely benign not specified 2017-05-15 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.
Invitae RCV000544406 SCV000637834 likely benign Hereditary diffuse gastric adenocarcinoma 2023-10-13 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000580440 SCV000684464 likely benign Hereditary cancer-predisposing syndrome 2016-05-29 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000421124 SCV002014996 uncertain significance not specified 2022-11-21 criteria provided, single submitter clinical testing Variant summary: CDH1 c.49-8C>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 2.6e-05 in 156612 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.49-8C>A in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.

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