Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000212114 | SCV000209834 | uncertain significance | not provided | 2021-12-22 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV000159806 | SCV000218083 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-20 | criteria provided, single submitter | clinical testing | The p.R150Q variant (also known as c.449G>A), located in coding exon 4 of the BARD1 gene, results from a G to A substitution at nucleotide position 449. The arginine at codon 150 is replaced by glutamine, 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. |
| Labcorp Genetics |
RCV000196853 | SCV000254581 | uncertain significance | Familial cancer of breast | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 150 of the BARD1 protein (p.Arg150Gln). This variant is present in population databases (rs730881412, gnomAD 0.01%). 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: 182037). 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, |
RCV000159806 | SCV000682790 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-02 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 150 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 performed for this variant. In a large breast cancer case-control meta analysis, this variant was identified in 1/60465 cases and was absent from the unaffected control cohort (PMID: 33471991; Leiden Open Variation Database DB-ID BARD1_000439). This variant has been identified in 6/250782 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226223 | SCV003922676 | uncertain significance | not specified | 2023-03-13 | criteria provided, single submitter | clinical testing | Variant summary: BARD1 c.449G>A (p.Arg150Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 250782 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.449G>A in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Baylor Genetics | RCV000196853 | SCV004217206 | uncertain significance | Familial cancer of breast | 2023-08-06 | criteria provided, single submitter | clinical testing |