Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328192 | SCV001943360 | likely benign | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-17 | reviewed by expert panel | curation | The c.1865A>G (p.Asn622Ser) missense variant has a frequency of 0.000007953 (2 of 251,480) in the gnomAD v2.1.1 cohort, with a maximum non-founder allele frequency of 0.00006152 (1 of 16,256) in the African subpopulation (http://gnomad.broadinstitute.org). This variant has been observed in >10 (27) individuals w/o DCG, SRC tumors, or LBC & whose families do not suggest HDGC (BS2; SCV000166547.6, SCV000329232.7). In summary, the clinical significance of this variant is classified as likely benign based on BS2 alone. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2. |
Labcorp Genetics |
RCV000123241 | SCV000166547 | likely benign | Hereditary diffuse gastric adenocarcinoma | 2024-01-28 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000131244 | SCV000186201 | likely benign | Hereditary cancer-predisposing syndrome | 2021-11-18 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Gene |
RCV000286705 | SCV000329232 | uncertain significance | not provided | 2024-02-20 | 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; This variant is associated with the following publications: (PMID: 15235021, 22850631, 33471991, 36436516) |
Counsyl | RCV000123241 | SCV000488709 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2016-05-25 | criteria provided, single submitter | clinical testing | |
St. |
RCV000123241 | SCV000890923 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2020-09-09 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000286705 | SCV001134069 | likely benign | not provided | 2022-09-08 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000131244 | SCV001348201 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-17 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 622 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CDH1-related disorders in the literature. This variant has been identified in 2/251480 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001824619 | SCV002074187 | uncertain significance | not specified | 2022-01-10 | criteria provided, single submitter | clinical testing | |
European Reference Network on Genetic Tumour Risk Syndromes |
RCV000123241 | SCV003926863 | likely benign | Hereditary diffuse gastric adenocarcinoma | 2022-08-01 | criteria provided, single submitter | clinical testing | BS2 (PMID: 30311375) |
Myriad Genetics, |
RCV000123241 | SCV004020021 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-03-06 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |