Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000570880 | SCV000668597 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-01-06 | criteria provided, single submitter | clinical testing | The p.T3306N variant (also known as c.9917C>A), located in coding exon 26 of the BRCA2 gene, results from a C to A substitution at nucleotide position 9917. The threonine at codon 3306 is replaced by asparagine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0004% (greater than 225000 alleles tested) in our clinical cohort. 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 p.T3306N remains unclear. |
Color Diagnostics, |
RCV000570880 | SCV004362847 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-18 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with asparagine at codon 3306 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 hereditary cancer 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. |