ClinVar Miner

Submissions for variant NM_032638.5(GATA2):c.1078T>A (p.Trp360Arg)

dbSNP: rs2107668680
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Pathology Research Laboratory, SA Pathology RCV001542234 SCV001760902 likely pathogenic Deafness-lymphedema-leukemia syndrome; GATA2 deficiency with susceptibility to MDS/AML 2021-07-06 criteria provided, single submitter curation PS4_Moderate, PM1, PM2, PM5, PP3
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV004785270 SCV005402149 pathogenic GATA2 deficiency with susceptibility to MDS/AML 2024-04-13 criteria provided, single submitter clinical testing The GATA2 c.1078T>A (p.Trp360Arg) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a deleterious effect on protein function, but this prediction has not been confirmed by functional studies. This variant has been reported in individuals with GATA2-deficiency (PMID: 25239263, 27577878, 28126493, 34893945). A variant affecting the same amino acid residue, p.Trp360Leu, was reported in a patient with GATA2-deficiency (PMID: 29146883). In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. In summary, this variant meets criteria to be classified as pathogenic
Labcorp Genetics (formerly Invitae), Labcorp RCV005225425 SCV005863266 uncertain significance Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections 2024-12-02 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 360 of the GATA2 protein (p.Trp360Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with GATA2-related conditions (PMID: 25239263, 27577878, 28126493, 34387894, 34893945). ClinVar contains an entry for this variant (Variation ID: 1184247). 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) 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.

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