Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000509922 | SCV000608156 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-10 | criteria provided, single submitter | clinical testing | The p.L3333P variant (also known as c.9998T>C), located in coding exon 26 of the BRCA2 gene, results from a T to C substitution at nucleotide position 9998. The leucine at codon 3333 is replaced by proline, an amino acid with similar properties. This amino acid position is not 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. |
| Invitae | RCV002527394 | SCV002929791 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-05-07 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. ClinVar contains an entry for this variant (Variation ID: 441460). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 3333 of the BRCA2 protein (p.Leu3333Pro). 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. |
| Baylor Genetics | RCV003464100 | SCV004213597 | uncertain significance | Familial cancer of breast | 2023-09-08 | criteria provided, single submitter | clinical testing | |
| MGZ Medical Genetics Center | RCV003464100 | SCV004543924 | likely benign | Familial cancer of breast | 2024-02-09 | criteria provided, single submitter | clinical testing | ACMG codes applied following ENIGMA VCEP rules: BP1_STR, PM2_SUP |
| All of Us Research Program, |
RCV004003580 | SCV004815796 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-02-24 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with proline at codon 3333 of the BRCA2 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 reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has not been identified 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. |