ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2251_2253del (p.Asn751del)

dbSNP: rs2152141513
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001893861 SCV002171892 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-08-31 criteria provided, single submitter clinical testing This variant, c.2251_2253del, results in the deletion of 1 amino acid(s) of the CDH1 protein (p.Asn751del), but otherwise preserves the integrity of the reading frame. 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: 1399691). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
GeneDx RCV002285511 SCV002576274 uncertain significance not provided 2022-09-21 criteria provided, single submitter clinical testing In-frame deletion of one amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Located in the critical cytoplasmic domain and the region of interaction with Hakai and p120-catenin (Brooks-Wilson et al., 2004; Figueiredo et al., 2013); Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15235021, 22850631)
Ambry Genetics RCV002449552 SCV002733442 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-24 criteria provided, single submitter clinical testing The c.2251_2253delAAC variant (also known as p.N751del) is located in coding exon 14 of the CDH1 gene. This variant results from an in-frame AAC deletion at nucleotide positions 2251 to 2253. This results in the in-frame deletion of an asparagine at codon 751. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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