ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2644G>A (p.Asp882Asn)

gnomAD frequency: 0.00009  dbSNP: rs200104963
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212394 SCV000149769 uncertain significance not provided 2020-03-13 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with breast cancer (Bonache 2018); This variant is associated with the following publications: (PMID: 29338689, 30306255)
Ambry Genetics RCV000115860 SCV000184064 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-03 criteria provided, single submitter clinical testing The p.D882N variant (also known as c.2644G>A), located in coding exon 16 of the CDH1 gene, results from a G to A substitution at nucleotide position 2644. The aspartic acid at codon 882 is replaced by asparagine, an amino acid with highly similar properties. This alteration has been reported in an individual with ductal carcinoma in situ diagnosed at age 29 with a family history of diffuse gastric cancer diagnosed at age 52 in a maternal cousin (Bonache S et al. J. Cancer Res. Clin. Oncol., 2018 Dec;144:2495-2513). This alteration has also been reported in breast cancer cases, as well as in controls (Momozawa Y et al. Nat Commun, 2018 10;9:4083; Dorling et al. N Engl J Med. 2021 02;384:428-439). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000232913 SCV000288478 likely benign Hereditary diffuse gastric adenocarcinoma 2024-01-21 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000115860 SCV000689523 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-03 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with asparagine at codon 882 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individuals affected with breast cancer, but also in unaffected individuals in the literature (PMID: 30287823, 30306255, 33471991). This variant has been identified in 15/282744 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Division of Medical Genetics, University of Washington RCV000232913 SCV001424797 uncertain significance Hereditary diffuse gastric adenocarcinoma 2019-08-09 criteria provided, single submitter clinical testing To our knowledge, this sequence variant has not been previously reported in the literature. The p.Asp882Asn variant has an overall allele frequency of 0.00005305 in the Broad Institute gnomAD Browser (https://gnomad.broadinstitute.org/). In silico analyses indicate that this variant may have a deleterious effect due to its relative conservation and predicted impact on the final protein product. It is unknown at this time whether this variant increases cancer risk; therefore, we consider it to be a variant of uncertain significance (VUS).
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212394 SCV001469751 uncertain significance not provided 2021-07-20 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000212394 SCV001714552 uncertain significance not provided 2020-08-05 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002465518 SCV002760871 uncertain significance not specified 2023-08-15 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 RCV000232913 SCV003926975 uncertain significance Hereditary diffuse gastric adenocarcinoma 2022-08-01 criteria provided, single submitter clinical testing Not applicable criteria (PMID: 30311375)
PreventionGenetics, part of Exact Sciences RCV003398713 SCV004104552 uncertain significance CDH1-related disorder 2023-04-04 criteria provided, single submitter clinical testing The CDH1 c.2644G>A variant is predicted to result in the amino acid substitution p.Asp882Asn. This variant has been reported with uncertain significance in an individual with breast/ovarian cancer (Bonache et al. 2018. PubMed ID: 30306255). This variant is reported in 0.020% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-68867397-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV003460831 SCV004215652 uncertain significance Familial cancer of breast 2023-09-02 criteria provided, single submitter clinical testing

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