Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000704865 | SCV000833836 | uncertain significance | Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections | 2023-06-27 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 581129). This missense change has been observed in individual(s) with clinical features of GATA2 deficiency (PMID: 30578959). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 346 of the GATA2 protein (p.Gly346Ser). 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. 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. |
Molecular Pathology Research Laboratory, |
RCV001541976 | SCV001760611 | uncertain significance | Deafness-lymphedema-leukemia syndrome; GATA2 deficiency with susceptibility to MDS/AML | 2021-07-06 | criteria provided, single submitter | curation | PS4_Supporting, PM2, PP3 |
Genetic Services Laboratory, |
RCV001816732 | SCV002068894 | uncertain significance | not specified | 2018-03-27 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV005338332 | SCV006007581 | uncertain significance | Inborn genetic diseases | 2025-02-27 | criteria provided, single submitter | clinical testing | The p.G346S variant (also known as c.1036G>A), located in coding exon 4 of the GATA2 gene, results from a G to A substitution at nucleotide position 1036. The glycine at codon 346 is replaced by serine, an amino acid with similar properties. This variant was reported in a 20-year-old proband with GATA2 deficiency-related bone marrow and immunodeficiency disorder (McReynolds LJ et al. Leuk Res, 2019 Jan;76:70-75). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |