ClinVar Miner

Submissions for variant NM_001145661.2(GATA2):c.1061C>T (p.Thr354Met) (rs387906631)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000706855 SCV000835929 pathogenic Lymphedema, primary, with myelodysplasia; Dendritic cell, monocyte, B lymphocyte, and natural killer lymphocyte deficiency 2018-01-24 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 354 of the GATA2 protein (p.Thr354Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with myelodysplastic syndrome and acute myeloid leukemia in several large families (PMID: 21892162, 21670465). Additionally, this variant has been reported in a patient with GATA2 deficiency (PMID: 23365458). ClinVar contains an entry for this variant (Variation ID: 29711). Experimental studies have shown that this missense change reduces GATA2 transactivation ability and inhibits apoptosis while enabling cell proliferation and survival (PMID: 21892162, 25676417). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics,PreventionGenetics RCV000984820 SCV001132702 pathogenic not provided 2015-07-23 criteria provided, single submitter clinical testing
Molecular Pathology Research Laboratory,SA Pathology RCV001542226 SCV001760894 pathogenic Lymphedema, primary, with myelodysplasia; GATA2 deficiency with susceptibility to MDS/AML 2021-07-06 criteria provided, single submitter curation PS3, PS4, PM1, PM2, PM5, PP1_Strong, PP3
GeneDx RCV000984820 SCV001785631 pathogenic not provided 2021-01-11 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect: NK-cell deficiency, reduced transactivation activity, reduced DNA binding activity (Hahn 2011, Kazenwadel 2012, Mace 2013, Hahn 2015); Not observed in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32888943, 33510405, 21892162, 27577878, 22271902, 22533337, 22147895, 24754962, 23223431, 21670465, 24227816, 29749400, 32098966, 31035956, 30232126, 29588856, 21765025, 25676417, 23365458)
OMIM RCV000022561 SCV000043850 pathogenic Dendritic cell, monocyte, B lymphocyte, and natural killer lymphocyte deficiency 2011-09-08 no assertion criteria provided literature only
OMIM RCV000022562 SCV000043851 risk factor Myelodysplastic syndrome 2011-09-08 no assertion criteria provided literature only
OMIM RCV000022563 SCV000043852 risk factor Leukemia, acute myeloid, susceptibility to 2011-09-08 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426616 SCV000504647 likely pathogenic Acute myeloid leukemia 2014-10-02 no assertion criteria provided literature only

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