Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000130149 | SCV000184983 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-25 | criteria provided, single submitter | clinical testing | The p.T2350I variant (also known as c.7049C>T), located in coding exon 13 of the BRCA2 gene, results from a C to T substitution at nucleotide position 7049. The threonine at codon 2350 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly 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. |
All of Us Research Program, |
RCV004804148 | SCV005424567 | uncertain significance | BRCA2-related cancer predisposition | 2024-05-14 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with isoleucine at codon 2350 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function. A functional study in Brca2-deficient mouse embryonic stem cells has shown that this variant does not impact cell viability or response to cisplatin or olaparib (PMID: 37922907). This variant has been reported in an individual affected with breast cancer (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_008567). 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. |