ClinVar Miner

Submissions for variant NM_000465.4(BARD1):c.2167C>G (p.His723Asp)

gnomAD frequency: 0.00001  dbSNP: rs1245669447
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001063764 SCV001228625 uncertain significance Familial cancer of breast 2022-07-11 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 857984). 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 histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 723 of the BARD1 protein (p.His723Asp).
Color Diagnostics, LLC DBA Color Health RCV001180973 SCV001346026 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-12 criteria provided, single submitter clinical testing This missense variant replaces histidine with aspartic acid at codon 723 of the BARD1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001180973 SCV002729211 uncertain significance Hereditary cancer-predisposing syndrome 2015-10-21 criteria provided, single submitter clinical testing The p.H723D variant (also known as c.2167C>G), located in coding exon 11 of the BARD1 gene, results from a C to G substitution at nucleotide position 2167. The histidine at codon 723 is replaced by aspartic acid, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 65000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. 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 p.H723D remains unclear.

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