Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000167326 | SCV000218176 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-12-08 | criteria provided, single submitter | clinical testing | The p.R3302S variant (also known as c.9906G>T), located in coding exon 26 of the BRCA2 gene, results from a G to T substitution at nucleotide position 9906. The arginine at codon 3302 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly 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. |
All of Us Research Program, |
RCV004804774 | SCV004846245 | uncertain significance | BRCA2-related cancer predisposition | 2024-07-20 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with serine at codon 3302 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 cancer in the literature, but it has been reported in an unaffected individual (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_008805). 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. |
Prevention |
RCV004732731 | SCV005360351 | uncertain significance | BRCA2-related disorder | 2024-08-29 | no assertion criteria provided | clinical testing | The BRCA2 c.9906G>T variant is predicted to result in the amino acid substitution p.Arg3302Ser. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. The variant has an interpretation of uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/187584/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |