Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory of Molecular Diagnosis of Cancer, |
RCV000240763 | SCV000265931 | uncertain significance | Breast neoplasm | 2015-11-01 | criteria provided, single submitter | research | |
Ambry Genetics | RCV000572755 | SCV000665085 | likely benign | Hereditary cancer-predisposing syndrome | 2017-11-28 | 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. |
Color Diagnostics, |
RCV000572755 | SCV000913979 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-11 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001239569 | SCV001412452 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 488 of the BRCA2 protein (p.Ile488Val). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with breast cancer (PMID: 27257965). ClinVar contains an entry for this variant (Variation ID: 224457). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. 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. |
University of Washington Department of Laboratory Medicine, |
RCV000572755 | SCV003851407 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
St. |
RCV003444220 | SCV004171487 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-10-18 | criteria provided, single submitter | clinical testing | The BRCA2 c.1462A>G (p.Ile488Val) missense change has a maximum founder subpopulation frequency of 0.004% and a maximum non-founder subpopulation frequency of 0.0007% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. This variant has been reported in individuals with breast cancer (PMID: 27257965, 30400234). To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |