ClinVar Miner

Submissions for variant NM_000465.4(BARD1):c.1016G>C (p.Ser339Thr)

dbSNP: rs201261729
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000539750 SCV000632927 uncertain significance Familial cancer of breast 2025-01-21 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 339 of the BARD1 protein (p.Ser339Thr). This variant is present in population databases (rs201261729, gnomAD 0.0009%). 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: 460685). 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 have shown that this missense change does not substantially affect 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.
Color Diagnostics, LLC DBA Color Health RCV000776214 SCV000911373 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-13 criteria provided, single submitter clinical testing This missense variant replaces serine with threonine at codon 339 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. An experimental functional study has shown this variant to be neutral in a homology directed recombination (HDR) assay (PMID: 30925164). This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251180 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.
Ambry Genetics RCV000776214 SCV002646593 likely benign Hereditary cancer-predisposing syndrome 2021-12-14 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.

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