ClinVar Miner

Submissions for variant NM_000465.4(BARD1):c.1571A>G (p.Asn524Ser)

gnomAD frequency: 0.00001  dbSNP: rs587781887
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130217 SCV000185056 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-25 criteria provided, single submitter clinical testing The p.N524S variant (also known as c.1571A>G), located in coding exon 7 of the BARD1 gene, results from an A to G substitution at nucleotide position 1571. The asparagine at codon 524 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV000212132 SCV000209828 uncertain significance not provided 2018-05-08 criteria provided, single submitter clinical testing This variant is denoted BARD1 c.1571A>G at the cDNA level, p.Asn524Ser (N524S) at the protein level, and results in the change of an Asparagine to a Serine (AAT>AGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BARD1 Asn524Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the Ankyrin 3 repeat region (Fox 2008). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BARD1 Asn524Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000457191 SCV000545594 uncertain significance Familial cancer of breast 2023-11-21 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 524 of the BARD1 protein (p.Asn524Ser). This variant is present in population databases (rs587781887, gnomAD 0.004%). 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: 141624). 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 disruptive. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 RCV000130217 SCV001340934 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-21 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000130217 SCV002527022 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-29 criteria provided, single submitter curation
Baylor Genetics RCV000457191 SCV004217223 uncertain significance Familial cancer of breast 2023-07-20 criteria provided, single submitter clinical testing

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