Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328219 | SCV004035097 | likely benign | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-18 | reviewed by expert panel | curation | The c.223T>C (p.Phe75Leu) missense variant has a frequency of 0.000003977 (1 of 251,418) in the gnomAD v2.1.1 cohort, with a maximum non-founder allele frequency of 0.000008795 (1 of 113,700) in the Non-Finnish European population (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been observed in at least 10 individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2). In summary, the clinical significance of this variant is classified as of likely benign based the ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PM2_supporting, BS2. |
Ambry Genetics | RCV000130841 | SCV000185739 | likely benign | Hereditary cancer-predisposing syndrome | 2016-02-09 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |
Invitae | RCV000554536 | SCV000637786 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-08-07 | criteria provided, single submitter | clinical testing | 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 142040). This missense change has been observed in individual(s) with breast cancer (PMID: 31871109). This variant is present in population databases (rs587782193, gnomAD 0.0009%). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 75 of the CDH1 protein (p.Phe75Leu). |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800438 | SCV002046825 | uncertain significance | not provided | 2021-04-01 | criteria provided, single submitter | clinical testing |