Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory of Molecular Diagnosis of Cancer, |
RCV000240754 | SCV000265968 | uncertain significance | Breast neoplasm | 2015-11-01 | criteria provided, single submitter | research | |
| Ambry Genetics | RCV000509951 | SCV000608188 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-23 | criteria provided, single submitter | clinical testing | The p.R3384G variant (also known as c.10150C>G), located in coding exon 26 of the BRCA2 gene, results from a C to G substitution at nucleotide position 10150. The arginine at codon 3384 is replaced by glycine, an amino acid with dissimilar properties. This alteration was identified in 1/507 unselected Chinese breast cancer patients (Zhong X et al. PLoS ONE, 2016 Jun;11:e0156789). 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. |
| Counsyl | RCV000663192 | SCV000786367 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2018-04-18 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001853358 | SCV002132317 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-07-29 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 3384 of the BRCA2 protein (p.Arg3384Gly). This variant is not present in population databases (gnomAD no frequency). 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: 224478). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 27257965, 30702160). |
| All of Us Research Program, |
RCV000663192 | SCV004846271 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-04-03 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glycine at codon 3384 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 been reported in 2 individuals affected with ovarian cancer and 1 individual affected with breast cancer (PMID: 33078592, 34178674, 33471991; Leiden Open Variation Database DB-ID BRCA2_006980). 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. |