Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001213428 | SCV001385057 | uncertain significance | Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections | 2023-08-28 | criteria provided, single submitter | clinical testing | 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GATA2 protein function. ClinVar contains an entry for this variant (Variation ID: 943269). This variant has not been reported in the literature in individuals affected with GATA2-related conditions. This variant is present in population databases (rs751678435, gnomAD 0.007%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 179 of the GATA2 protein (p.Lys179Arg). |