Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000579408 | SCV000682788 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-23 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000635835 | SCV000757260 | uncertain significance | Familial cancer of breast | 2023-11-04 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 148 of the BARD1 protein (p.Ser148Asn). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 489672). 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 disruptive. 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. |
| Ambry Genetics | RCV000579408 | SCV001184226 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-18 | criteria provided, single submitter | clinical testing | The p.S148N variant (also known as c.443G>A), located in coding exon 4 of the BARD1 gene, results from a G to A substitution at nucleotide position 443. The serine at codon 148 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800797 | SCV002047173 | uncertain significance | not provided | 2023-09-05 | criteria provided, single submitter | clinical testing | This variant has not been reported as a germline variant in the published literature. In a large-scale breast cancer association study, this variant was observed in a control individual and not in any breast cancer cases (see LOVD (http://databases.lovd.nl/shared/genes/BARD1) and PMID: 33471991 (2021)). The frequency of this variant in the general population, 0.00014 (5/34502 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Gene |
RCV001800797 | SCV003845597 | uncertain significance | not provided | 2023-03-22 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 33692861, Wang2022[abstract]) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003387890 | SCV004099676 | uncertain significance | not specified | 2023-09-09 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000635835 | SCV004217241 | uncertain significance | Familial cancer of breast | 2023-06-25 | criteria provided, single submitter | clinical testing |