chr3-128485837-G-A

Position:

• chr3-128485837-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032638.5(GATA2):​c.761C>T​(p.Pro254Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GATA2 NM_032638.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 7.25

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29160407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA2	NM_032638.5	c.761C>T	p.Pro254Leu	missense_variant	3/6	ENST00000341105.7	NP_116027.2
GATA2	NM_001145661.2	c.761C>T	p.Pro254Leu	missense_variant	4/7		NP_001139133.1
GATA2	NM_001145662.1	c.761C>T	p.Pro254Leu	missense_variant	3/6		NP_001139134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7	c.761C>T	p.Pro254Leu	missense_variant	3/6	1	NM_032638.5	ENSP00000345681.2
GATA2	ENST00000487848.6	c.761C>T	p.Pro254Leu	missense_variant	4/7	1		ENSP00000417074.1
GATA2	ENST00000430265.6	c.761C>T	p.Pro254Leu	missense_variant	3/6	1		ENSP00000400259.2
GATA2	ENST00000696466.1	c.1043C>T	p.Pro348Leu	missense_variant	5/8			ENSP00000512647.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Monocytopenia with susceptibility to infections Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 08, 2011

- -

Deafness-lymphedema-leukemia syndrome;CN300066:GATA2 deficiency with susceptibility to MDS/AML Uncertain:1

Uncertain significance, criteria provided, single submitter

curation

Molecular Pathology Research Laboratory, SA Pathology

Jul 06, 2021

PS4_Supporting, PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;.;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.093
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	.;D;D
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Uncertain	0.24	D
MutationAssessor	Benign	0.79	N;N;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Uncertain	0.54
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.0020	B;B;B
Vest4		0.30
MutPred		0.38		Gain of glycosylation at Y252 (P = 0.0115);Gain of glycosylation at Y252 (P = 0.0115);Gain of glycosylation at Y252 (P = 0.0115);
MVP		0.97
MPC		1.5
ClinPred		0.90	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.74

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

Other links and lift over

dbSNP: rs387906630; hg19: chr3-128204680;