Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000197341 | SCV000254203 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-07-20 | 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. 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: 91467). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is present in population databases (rs398122574, gnomAD 0.007%). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 2324 of the BRCA2 protein (p.His2324Arg). |
| Ambry Genetics | RCV001025862 | SCV001188133 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-22 | criteria provided, single submitter | clinical testing | The p.H2324R variant (also known as c.6971A>G), located in coding exon 12 of the BRCA2 gene, results from an A to G substitution at nucleotide position 6971. The histidine at codon 2324 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well 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. |
| Myriad Genetics, |
RCV000076984 | SCV004018648 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-06-02 | criteria provided, single submitter | clinical testing | This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. |
| All of Us Research Program, |
RCV000076984 | SCV004844337 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2024-01-11 | criteria provided, single submitter | clinical testing | This missense variant replaces histidine with arginine at codon 2324 of the BRCA2 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in an individual affected with breast cancer (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_008548). This variant has been identified in 1/250320 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. |
| Sharing Clinical Reports Project |
RCV000076984 | SCV000108781 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2012-12-28 | no assertion criteria provided | clinical testing |