Submissions for variant NM_032638.5(GATA2):c.1024G>A (p.Ala342Thr)

gnomAD frequency: 0.00001  dbSNP: rs751285156

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000808036	SCV000948120	uncertain significance	Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections	2025-02-02	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 342 of the GATA2 protein (p.Ala342Thr). This variant is present in population databases (rs751285156, gnomAD 0.006%). This missense change has been observed in individual(s) with acute myeloid leukemia (PMID: 24033149). ClinVar contains an entry for this variant (Variation ID: 652480). 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.
Molecular Pathology Research Laboratory, SA Pathology	RCV001541975	SCV001760610	uncertain significance	Deafness-lymphedema-leukemia syndrome; GATA2 deficiency with susceptibility to MDS/AML	2021-07-06	criteria provided, single submitter	curation	No criteria satisfied
Baylor Genetics	RCV003461176	SCV004198621	uncertain significance	Acute myeloid leukemia	2023-09-21	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005036177	SCV005659414	uncertain significance	Acute myeloid leukemia; Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections; Myelodysplastic syndrome	2024-03-07	criteria provided, single submitter	clinical testing
Clinical Genomics Laboratory, Washington University in St. Louis	RCV005051833	SCV005685474	uncertain significance	Deafness-lymphedema-leukemia syndrome	2024-06-26	criteria provided, single submitter	clinical testing	A GATA2 c.1024G>A (p.Ala342Thr) variant was identified at a near heterozygous allelic fraction of 48.8%, a frequency which may be consistent with it being of germline origin. This variant has been reported in a germline state in a patient with de novo pediatric acute myeloid leukemia (Shiba N et al., PMID: 24033149). This variant is observed on 35/1,613,364 alleles in the general population (gnomAD v4.1.0). Computational predictors are uncertain as to the impact of this variant on GATA2 function. Due to limited information and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.
GeneDx	RCV005225155	SCV005870465	uncertain significance	not provided	2024-08-20	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; Observed as a germline variant in an individual with pediatric acute myeloid leukemia (AML) (PMID: 24033149); This variant is associated with the following publications: (PMID: 25707267, 24033149)