ClinVar Miner

Submissions for variant NM_032638.5(GATA2):c.1085G>A (p.Arg362Gln)

dbSNP: rs867160952
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV000761281 SCV000891240 likely pathogenic Deafness-lymphedema-leukemia syndrome 2016-11-07 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001508505 SCV001714707 likely pathogenic not provided 2020-03-23 criteria provided, single submitter clinical testing PS4_Moderate, PM1, PM2, PP3
Labcorp Genetics (formerly Invitae), Labcorp RCV002533864 SCV003445468 uncertain significance Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections 2024-01-09 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 362 of the GATA2 protein (p.Arg362Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of GATA2-related conditions (PMID: 31309983, 32682923). ClinVar contains an entry for this variant (Variation ID: 623173). 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%. Experimental studies have shown that this missense change affects GATA2 function (PMID: 26214525). 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.
Ambry Genetics RCV005338345 SCV006000768 likely pathogenic Inborn genetic diseases 2025-03-12 criteria provided, single submitter clinical testing The p.R362Q variant (also known as c.1085G>A), located in coding exon 4 of the GATA2 gene, results from a G to A substitution at nucleotide position 1085. The arginine at codon 362 is replaced by glutamine, an amino acid with highly similar properties. This variant was reported in individual(s) with features consistent with GATA2 deficiency syndrome (Weinberg OK et al. Am J Clin Pathol, 2019 Aug;152:258-276; van Lier YF et al. Clin Immunol, 2020 Sep;218:108522). This missense variant is located in a region that has a low rate of benign missense variation (Lek M et al. Nature. 2016 Aug 18;536(7616):285-91; DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Firth H.V. et al. 2009. Am.J.Hum.Genet. 84, 524-533 (DOI: dx.doi.org/10/1016/j.ajhg.2009.03.010)). 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 majority of available evidence to date, this variant is likely to be pathogenic.

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