Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000691681 | SCV000819470 | uncertain significance | Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections | 2024-06-10 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 457 of the GATA2 protein (p.Thr457Met). This variant is present in population databases (rs139415862, gnomAD 0.007%). This missense change has been observed in individual(s) with pancreatic cancer (PMID: 31958074). ClinVar contains an entry for this variant (Variation ID: 570747). 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) performed at Invitae indicates that this missense variant is expected to disrupt GATA2 protein function with a positive predictive value of 95%. 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 |
RCV002264975 | SCV002547205 | uncertain significance | not provided | 2022-01-10 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31958074) |
| Prevention |
RCV003411607 | SCV004109855 | uncertain significance | GATA2-related disorder | 2023-02-21 | criteria provided, single submitter | clinical testing | The GATA2 c.1370C>T variant is predicted to result in the amino acid substitution p.Thr457Met. This variant was reported along with other variants in an individual with pancreatic cancer (Supplement, Ma et al. 2020. PubMed ID: 31958074). I has also been reported in a GAT2 variant study in the context of myeloid leukemia (Table S5, referred to as rs139415862, Celton et al. 2014. PubMed ID: 24514424). This variant is reported in 0.0066% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-128199935-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Baylor Genetics | RCV004569302 | SCV005058892 | uncertain significance | Acute myeloid leukemia | 2024-02-27 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004972859 | SCV005596777 | uncertain significance | Inborn genetic diseases | 2024-10-17 | criteria provided, single submitter | clinical testing | The p.T457M variant (also known as c.1370C>T), located in coding exon 5 of the GATA2 gene, results from a C to T substitution at nucleotide position 1370. The threonine at codon 457 is replaced by methionine, an amino acid with similar properties. 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. |