ClinVar Miner

Submissions for variant NM_032638.5(GATA2):c.1061C>T (p.Thr354Met)

dbSNP: 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 Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections 2022-11-15 criteria provided, single submitter clinical testing Experimental studies have shown that this missense change affects GATA2 function (PMID: 21892162, 25676417). For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 29711). This missense change has been observed in individual(s) with GATA2 deficiency and myelodysplastic syndrome and acute myeloid leukemia (PMID: 21670465, 21892162, 23365458). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 354 of the GATA2 protein (p.Thr354Met).
PreventionGenetics, part of Exact Sciences RCV000984820 SCV001132702 pathogenic not provided 2015-07-23 criteria provided, single submitter clinical testing
Molecular Pathology Research Laboratory, SA Pathology RCV001542226 SCV001760894 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_Strong, PP3
GeneDx RCV000984820 SCV001785631 pathogenic not provided 2022-06-13 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 at significant frequency in large population cohorts (gnomAD); 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: 29749400, 23365458, 25676417, 21892162, 22147895, 21765025, 29588856, 30232126, 31035956, 32098966, 24227816, 21670465, 23223431, 24754962, 22533337, 22271902, 27577878, 1714909, 28179282, 33510405, 32888943)
OMIM RCV000022561 SCV000043850 pathogenic Monocytopenia with susceptibility to infections 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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