chr3-128485869-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032638.5(GATA2):​c.729C>G​(p.His243Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GATA2
NM_032638.5 missense

Scores

5
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45
Variant links:
Genes affected
GATA2 (HGNC:4171): (GATA binding protein 2) This gene encodes a member of the GATA family of zinc-finger transcription factors that are named for the consensus nucleotide sequence they bind in the promoter regions of target genes. The encoded protein plays an essential role in regulating transcription of genes involved in the development and proliferation of hematopoietic and endocrine cell lineages. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GATA2NM_001145661.2 linkuse as main transcriptc.729C>G p.His243Gln missense_variant 4/7 ENST00000487848.6 NP_001139133.1
GATA2NM_032638.5 linkuse as main transcriptc.729C>G p.His243Gln missense_variant 3/6 ENST00000341105.7 NP_116027.2
GATA2NM_001145662.1 linkuse as main transcriptc.729C>G p.His243Gln missense_variant 3/6 NP_001139134.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GATA2ENST00000341105.7 linkuse as main transcriptc.729C>G p.His243Gln missense_variant 3/61 NM_032638.5 ENSP00000345681 P1P23769-1
GATA2ENST00000487848.6 linkuse as main transcriptc.729C>G p.His243Gln missense_variant 4/71 NM_001145661.2 ENSP00000417074 P1P23769-1
GATA2ENST00000430265.6 linkuse as main transcriptc.729C>G p.His243Gln missense_variant 3/61 ENSP00000400259 P23769-2
GATA2ENST00000696466.1 linkuse as main transcriptc.1011C>G p.His337Gln missense_variant 5/8 ENSP00000512647

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpApr 07, 2023In 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. 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. ClinVar contains an entry for this variant (Variation ID: 577683). This variant has not been reported in the literature in individuals affected with GATA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 243 of the GATA2 protein (p.His243Gln). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.80
D;.;D
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.18
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.78
.;T;T
M_CAP
Pathogenic
0.31
D
MetaRNN
Uncertain
0.62
D;D;D
MetaSVM
Uncertain
0.43
D
MutationAssessor
Benign
1.5
L;L;L
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-3.5
D;D;D
REVEL
Uncertain
0.59
Sift
Benign
0.054
T;T;T
Sift4G
Benign
0.097
T;T;T
Polyphen
0.040
B;B;B
Vest4
0.88
MutPred
0.22
Loss of glycosylation at T238 (P = 0.036);Loss of glycosylation at T238 (P = 0.036);Loss of glycosylation at T238 (P = 0.036);
MVP
0.97
MPC
1.4
ClinPred
0.92
D
GERP RS
1.8
Varity_R
0.54
gMVP
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs369673069; hg19: chr3-128204712; API