ClinVar Miner

Submissions for variant NM_000465.4(BARD1):c.2179G>A (p.Asp727Asn) (rs730881424)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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 2020-09-18 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 2020-10-30 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 727 of the BARD1 protein (p.Asp727Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs730881424, ExAC 0.03%). This variant has not been reported in the literature in individuals with BARD1-related disease. 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: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The asparagine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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,PreventionGenetics RCV000679340 SCV000806119 uncertain significance not provided 2017-05-04 criteria provided, single submitter clinical testing
Color Health, Inc RCV000570038 SCV000903286 likely benign Hereditary cancer-predisposing syndrome 2016-11-07 criteria provided, single submitter clinical testing

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