Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001049661 | SCV001213726 | uncertain significance | Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections | 2025-01-21 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 62 of the GATA2 protein (p.Asn62Lys). This variant is present in population databases (rs751200779, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with GATA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 846368). Invitae Evidence 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 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. |
| Gene |
RCV003328647 | SCV004035860 | uncertain significance | not provided | 2023-03-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Prevention |
RCV003405250 | SCV004116271 | uncertain significance | GATA2-related disorder | 2023-01-19 | criteria provided, single submitter | clinical testing | The GATA2 c.186C>G variant is predicted to result in the amino acid substitution p.Asn62Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0065% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-128205689-G-C) and has been interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/846368). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Baylor Genetics | RCV004570177 | SCV005058911 | uncertain significance | Acute myeloid leukemia | 2023-11-17 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV005338531 | SCV006007579 | uncertain significance | Inborn genetic diseases | 2025-01-13 | criteria provided, single submitter | clinical testing | The p.N62K variant (also known as c.186C>G), located in coding exon 1 of the GATA2 gene, results from a C to G substitution at nucleotide position 186. The asparagine at codon 62 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |