ClinVar Miner

Submissions for variant NM_000465.4(BARD1):c.1479A>C (p.Gln493His)

gnomAD frequency: 0.00006  dbSNP: rs375029767
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223436 SCV000273818 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-24 criteria provided, single submitter clinical testing The p.Q493H variant (also known as c.1479A>C), located in coding exon 6 of the BARD1 gene, results from an A to C substitution at nucleotide position 1479. The glutamine at codon 493 is replaced by histidine, an amino acid with highly similar properties. This variant was reported in 4/60,466 breast cancer cases and in 5/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This amino acid position is 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 RCV000475623 SCV000545622 uncertain significance Familial cancer of breast 2023-12-05 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 493 of the BARD1 protein (p.Gln493His). This variant is present in population databases (rs375029767, 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: 230313). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Color Diagnostics, LLC DBA Color Health RCV000223436 SCV000911379 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-01 criteria provided, single submitter clinical testing This missense variant replaces glutamine with histidine at codon 493 of the BARD1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 6/282754 chromosomes 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.
GeneDx RCV003441793 SCV004170098 uncertain significance not provided 2023-10-13 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Observed in both cases and controls in a breast cancer study (Dorling et al., 2021); This variant is associated with the following publications: (PMID: 18480049, 33471991)

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