Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164887 | SCV000215573 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-11 | criteria provided, single submitter | clinical testing | The p.S51L variant (also known as c.152C>T), located in coding exon 1 of the BARD1 gene, results from a C to T substitution at nucleotide position 152. The serine at codon 51 is replaced by leucine, an amino acid with dissimilar properties. 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 this alteration remains unclear. |
| Labcorp Genetics |
RCV000534515 | SCV000632964 | uncertain significance | Familial cancer of breast | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 51 of the BARD1 protein (p.Ser51Leu). This variant is present in population databases (rs766788652, gnomAD 0.003%). 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: 185459). 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. 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, |
RCV000164887 | SCV000682704 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-31 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with leucine at codon 51 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). A functional study has suggested that this variant may affect DNA damage response (PMID: 33606978). This variant has been reported in an individual affected with breast cancer (PMID: 33471991; Leiden Open Variation Database DB-ID BARD1_000482). This variant has been identified in 4/273836 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. |
| Gene |
RCV002510802 | SCV002820768 | uncertain significance | not provided | 2023-01-13 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies are inconclusive: base editing screens identified this variant as a VUS that exhibits likely pathogenic/pathogenic behavior (Cuella-Martin et al., 2021); This variant is associated with the following publications: (PMID: 18480049, 33606978) |
| Baylor Genetics | RCV000534515 | SCV004217202 | uncertain significance | Familial cancer of breast | 2024-02-07 | criteria provided, single submitter | clinical testing |