Submissions for variant NM_032638.5(GATA2):c.1187G>A (p.Arg396Gln)

dbSNP: rs1553770434

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000529588	SCV000651490	pathogenic	Deafness-lymphedema-leukemia syndrome; Monocytopenia with susceptibility to infections	2023-10-08	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 396 of the GATA2 protein (p.Arg396Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with GATA2 deficiency (PMID: 21670465, 22430350, 22533337, 23223431, 24077845, 25624456). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 472437). 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: 25624456). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences	RCV000984830	SCV001132713	pathogenic	not provided	2017-01-30	criteria provided, single submitter	clinical testing
Molecular Pathology Research Laboratory, SA Pathology	RCV001541953	SCV001760588	pathogenic	Deafness-lymphedema-leukemia syndrome; GATA2 deficiency with susceptibility to MDS/AML	2021-07-06	criteria provided, single submitter	curation	PS2, PS3, PS4, PM1, PM2, PM5, PP1_Moderate, PP3