Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000679340 | SCV000209858 | uncertain significance | not provided | 2018-07-09 | criteria provided, single submitter | clinical testing | This variant is denoted BARD1 c.2179G>A at the cDNA level, p.Asp727Asn (D727N) at the protein level, and results in the change of an Aspartic Acid to an Asparagine (GAT>AAT). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. BARD1 Asp727Asn was not observed at a significant allele frequency in large population cohorts (Lek 2016). BARD1 Asp727Asn is located in the BRCT2 domain (Fox 2008, UniProt). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available information, it is unclear whether BARD1 Asp727Asn is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000570038 | SCV000665700 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-28 | criteria provided, single submitter | clinical testing | The p.D727N variant (also known as c.2179G>A), located in coding exon 11 of the BARD1 gene, results from a G to A substitution at nucleotide position 2179. The aspartic acid at codon 727 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is not well 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. |
Invitae | RCV000635642 | SCV000757063 | uncertain significance | Familial cancer of breast | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 727 of the BARD1 protein (p.Asp727Asn). This variant is present in population databases (rs730881424, gnomAD 0.03%). 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: 182054). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
Preventiongenetics, |
RCV000679340 | SCV000806119 | uncertain significance | not provided | 2017-05-04 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000570038 | SCV000903286 | likely benign | Hereditary cancer-predisposing syndrome | 2016-11-07 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000679340 | SCV004222393 | uncertain significance | not provided | 2023-02-23 | criteria provided, single submitter | clinical testing | In the published literature, this variant has been reported along with a pathogenic BRAC2 variant in an individual with hypersensitivity to ionizing radiation (PMID: 34153142 (2021)). It has also been reported as a somatic variant detected in a stomach cancer tissue specimen (PMID: 29292755 (2017)). The frequency of this variant in the general population, 0.00025 (9/35430 chromosomes in Latino/Admixed American subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. 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. |