ClinVar Miner

Submissions for variant NM_032638.5(GATA2):c.1391G>T (p.Ser464Ile)

gnomAD frequency: 0.00004  dbSNP: rs770949428
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000473302 SCV000541497 uncertain significance Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections 2024-05-31 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 464 of the GATA2 protein (p.Ser464Ile). This variant is present in population databases (rs770949428, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with GATA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 404069). 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) has been performed at Invitae 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003228926 SCV002010686 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001821226 SCV002065625 uncertain significance not specified 2017-12-18 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003153574 SCV003843093 uncertain significance GATA2 deficiency with susceptibility to MDS/AML 2023-03-10 criteria provided, single submitter clinical testing The GATA2 c.1391G>T (p.Ser464Ile) missense change has a maximum subpopulation frequency of 0.014% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals presenting with GATA2-associated clinical phenotypes. 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.
GeneDx RCV003228926 SCV003926318 uncertain significance not provided 2022-11-17 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV001821226 SCV004243174 uncertain significance not specified 2025-03-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV004567939 SCV005058894 uncertain significance Acute myeloid leukemia 2024-02-17 criteria provided, single submitter clinical testing

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