Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001022589 | SCV001184343 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-21 | criteria provided, single submitter | clinical testing | The p.R15H variant (also known as c.44G>A), located in coding exon 1 of the BARD1 gene, results from a G to A substitution at nucleotide position 44. The arginine at codon 15 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV001022589 | SCV001351022 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-01 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with histidine at codon 15 of the BARD1 protein. Computational prediction tool 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. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/31370 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. |
Labcorp Genetics |
RCV001862223 | SCV002190623 | uncertain significance | Familial cancer of breast | 2023-04-10 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 824948). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 15 of the BARD1 protein (p.Arg15His). |
Baylor Genetics | RCV001862223 | SCV005053316 | uncertain significance | Familial cancer of breast | 2024-03-18 | criteria provided, single submitter | clinical testing |