Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000635727 | SCV000757148 | uncertain significance | Familial cancer of breast | 2022-10-13 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 530092). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 568 of the BARD1 protein (p.Gly568Ala). |
| St. |
RCV001775141 | SCV002012406 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-09-22 | criteria provided, single submitter | clinical testing | The BARD1 c.1703G>C (p.Gly568Ala) missense change is absent in gnomAD v2.1.1 (PM2_supporting; https://gnomad.broadinstitute.org/). It is also absent in a database of women older than 70 years of age who have never had cancer (https://whi.color.com/). Five of seven in silico tools predict a benign effect of this variant on protein function (BP4), but these predictions have not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with hereditary breast and ovarian cancer. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_supporting, BP4. |
| Ambry Genetics | RCV002406362 | SCV002715522 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-21 | criteria provided, single submitter | clinical testing | The p.G568A variant (also known as c.1703G>C), located in coding exon 8 of the BARD1 gene, results from a G to C substitution at nucleotide position 1703. The glycine at codon 568 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. 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 | RCV003478358 | SCV004221614 | uncertain significance | not provided | 2023-06-30 | criteria provided, single submitter | clinical testing | This variant has not been reported in individuals with BARD1-related conditions in the published literature. In a breast cancer case-control study, the variant has only been reported in unaffected control (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/BARD1)). It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |