Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001207341 | SCV001378686 | uncertain significance | Familial cancer of breast | 2019-08-23 | criteria provided, single submitter | clinical testing | 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BARD1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glycine at codon 729 of the BARD1 protein (p.Asp729Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |
Baylor Genetics | RCV001207341 | SCV004217251 | uncertain significance | Familial cancer of breast | 2023-06-16 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004033698 | SCV005035628 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-15 | criteria provided, single submitter | clinical testing | The p.D729G variant (also known as c.2186A>G), located in coding exon 11 of the BARD1 gene, results from an A to G substitution at nucleotide position 2186. The aspartic acid at codon 729 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |