ClinVar Miner

Submissions for variant NM_000465.4(BARD1):c.308G>A (p.Ser103Asn)

gnomAD frequency: 0.00019  dbSNP: rs145629242
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131209 SCV000186159 likely benign Hereditary cancer-predisposing syndrome 2020-10-31 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV000212110 SCV000209825 uncertain significance not provided 2023-10-27 criteria provided, single submitter clinical testing Published functional studies demonstrate homology-directed repair activity comparable to wild-type (PMID: 30925164); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 18480049, 14647430, 33471991, 35264596, 30925164)
Invitae RCV000200605 SCV000254580 uncertain significance Familial cancer of breast 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 103 of the BARD1 protein (p.Ser103Asn). This variant is present in population databases (rs145629242, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with breast cancer (PMID: 35264596). ClinVar contains an entry for this variant (Variation ID: 142216). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BARD1 function (PMID: 30925164). 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.
Mendelics RCV000200605 SCV000837983 uncertain significance Familial cancer of breast 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212110 SCV000887590 benign not provided 2022-05-04 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000131209 SCV000903490 likely benign Hereditary cancer-predisposing syndrome 2022-04-06 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000131209 SCV002529610 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-13 criteria provided, single submitter curation
PreventionGenetics, part of Exact Sciences RCV003407553 SCV004113224 uncertain significance BARD1-related disorder 2023-01-11 criteria provided, single submitter clinical testing The BARD1 c.308G>A variant is predicted to result in the amino acid substitution p.Ser103Asn. This variant was reported in an individual with cancer; however, in vitro analysis in a homology-directed repair assay indicated the resulting protein functioned similar to wild type (Adamovich et al. 2019. PubMed ID: 30925164). This variant is reported in 0.060% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-215657077-C-T). In ClinVar, this variant has been interpreted as 'uncertain' or 'likely benign' by outside laboratories (https://preview.ncbi.nlm.nih.gov/clinvar/variation/142216/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV000200605 SCV004214940 uncertain significance Familial cancer of breast 2023-10-30 criteria provided, single submitter clinical testing

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