ClinVar Miner

Submissions for variant NM_032638.5(GATA2):c.1192C>T (p.Arg398Trp)

dbSNP: rs387906629
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000502442 SCV000594916 pathogenic Leukemia, acute myeloid, susceptibility to 2016-06-14 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000984831 SCV001132714 pathogenic not provided 2016-10-09 criteria provided, single submitter clinical testing
Invitae RCV001384284 SCV001583727 pathogenic Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections 2023-07-07 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 29709). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 398 of the GATA2 protein (p.Arg398Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with GATA2 deficiency (PMID: 21670465, 21765025). 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. Experimental studies have shown that this missense change affects GATA2 function (PMID: 29882021). For these reasons, this variant has been classified as Pathogenic.
Molecular Pathology Research Laboratory, SA Pathology RCV001541956 SCV001760591 pathogenic Deafness-lymphedema-leukemia syndrome; GATA2 deficiency with susceptibility to MDS/AML 2021-07-06 criteria provided, single submitter curation PS3, PS4, PM1, PM2, PM5, PP1_Moderate, PP3
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000022559 SCV002577573 pathogenic Monocytopenia with susceptibility to infections 2022-02-17 criteria provided, single submitter clinical testing PS4, PM1, PM2, PM5, PP2, PP3, PP5
Mayo Clinic Laboratories, Mayo Clinic RCV000984831 SCV004226759 pathogenic not provided 2022-04-13 criteria provided, single submitter clinical testing PP3, PM1, PM2_supporting, PS3, PS4
Ambry Genetics RCV004018663 SCV005029320 pathogenic Inborn genetic diseases 2023-12-15 criteria provided, single submitter clinical testing The p.R398W pathogenic mutation (also known as c.1192C>T), located in coding exon 5 of the GATA2 gene, results from a C to T substitution at nucleotide position 1192. The arginine at codon 398 is replaced by tryptophan, an amino acid with dissimilar properties. This mutation has been detected in multiple unrelated individuals with GATA2 deficiency syndrome (Dickinson RE et al. Blood, 2011 Sep;118:2656-8; Hsu AP et al. Blood, 2011 Sep;118:2653-5; Churpek JE et al. Blood, 2015 Nov;126:2484-90; Mardahl M et al. Br J Haematol, 2019 Aug;186:471-476; West RR et al. Blood Adv, 2022 Feb;6:793-807). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
OMIM RCV000022559 SCV000043848 pathogenic Monocytopenia with susceptibility to infections 2011-09-08 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000445214 SCV000504646 likely pathogenic Acute myeloid leukemia 2014-10-02 no assertion criteria provided literature only

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