Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000823278 | SCV000964129 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2018-11-21 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA2-related disease. This sequence change replaces isoleucine with lysine at codon 2550 of the BRCA2 protein (p.Ile2550Lys). The isoleucine residue is weakly conserved and there is a moderate physicochemical difference between isoleucine and lysine. |
| Ambry Genetics | RCV002390705 | SCV002670706 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-29 | criteria provided, single submitter | clinical testing | The p.I2550K variant (also known as c.7649T>A), located in coding exon 15 of the BRCA2 gene, results from a T to A substitution at nucleotide position 7649. The isoleucine at codon 2550 is replaced by lysine, an amino acid with dissimilar properties. This amino acid position is poorly 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. |