ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2292C>A (p.Asp764Glu)

dbSNP: rs61747636
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215264 SCV000275625 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-08 criteria provided, single submitter clinical testing The p.D764E variant (also known as c.2292C>A), located in coding exon 14 of the CDH1 gene, results from a C to A substitution at nucleotide position 2292. The aspartic acid at codon 764 is replaced by glutamic acid, an amino acid with highly similar properties. This variant was reported in at least one individual with features consistent with CDH1-related diffuse gastric and lobular breast cancer (DGLBC) (Garcia-Pelaez J et al. Lancet Oncol, 2023 Jan;24:91-106; Lee CYC et al. Lancet Oncol, 2023 Jan;24:107-116). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001066681 SCV001231697 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-09-03 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 764 of the CDH1 protein (p.Asp764Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 231701). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health RCV000215264 SCV001356363 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-20 criteria provided, single submitter clinical testing
European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto RCV001066681 SCV003926914 uncertain significance Hereditary diffuse gastric adenocarcinoma 2022-08-01 criteria provided, single submitter clinical testing PM2 (PMID: 30311375)
Baylor Genetics RCV003462474 SCV004215680 uncertain significance Familial cancer of breast 2023-08-04 criteria provided, single submitter clinical testing
GeneDx RCV004721307 SCV005327343 uncertain significance not provided 2023-11-27 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in two individuals from one family meeting testing criteria for HDGC and considered a Variant of Unknown Significance by the authors (PMID: 36509094); This variant is associated with the following publications: (PMID: 36436516, 28688938, 15235021, 22850631, 36509094)

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