Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000538147 | SCV000651499 | uncertain significance | Lymphedema, primary, with myelodysplasia; Dendritic cell, monocyte, B lymphocyte, and natural killer lymphocyte deficiency | 2017-07-06 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with serine at codon 458 of the GATA2 protein (p.Pro458Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a GATA2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on GATA2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |