ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2267A>G (p.Asp756Gly)

dbSNP: rs2152141545
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001933225 SCV002190104 uncertain significance Hereditary diffuse gastric adenocarcinoma 2020-11-28 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with CDH1-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glycine at codon 756 of the CDH1 protein (p.Asp756Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine.
Ambry Genetics RCV002449587 SCV002733238 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-25 criteria provided, single submitter clinical testing The p.D756G variant (also known as c.2267A>G), located in coding exon 14 of the CDH1 gene, results from an A to G substitution at nucleotide position 2267. The aspartic acid at codon 756 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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