dbSNP rs770511115: GATA2:p.Gly272Val (chr3-128485783-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032638.5(GATA2):c.815G>T(p.Gly272Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GATA2
NM_032638.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.07

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]

GATA2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.758

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA2	NM_032638.5 link	c.815G>T	p.Gly272Val	missense_variant	Exon 3 of 6	ENST00000341105.7	NP_116027.2	P23769-1
GATA2	NM_001145661.2 link	c.815G>T	p.Gly272Val	missense_variant	Exon 4 of 7		NP_001139133.1	P23769-1
GATA2	NM_001145662.1 link	c.815G>T	p.Gly272Val	missense_variant	Exon 3 of 6		NP_001139134.1	P23769-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GATA2	ENST00000341105.7 link	c.815G>T	p.Gly272Val	missense_variant	Exon 3 of 6	1	NM_032638.5	ENSP00000345681.2	P23769-1
GATA2	ENST00000487848.6 link	c.815G>T	p.Gly272Val	missense_variant	Exon 4 of 7	1		ENSP00000417074.1	P23769-1
GATA2	ENST00000430265.6 link	c.815G>T	p.Gly272Val	missense_variant	Exon 3 of 6	1		ENSP00000400259.2	P23769-2
GATA2	ENST00000696466.1 link	c.1097G>T	p.Gly366Val	missense_variant	Exon 5 of 8			ENSP00000512647.1	A0A8Q3WLD0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461724

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.79

D;.;D

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

.;D;D

M_CAP

Pathogenic

0.41

MetaRNN

Pathogenic

0.76

D;D;D

MetaSVM

Pathogenic

0.94

MutationAssessor

Benign

1.8

L;L;L

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Pathogenic

0.74

Sift

Uncertain

0.015

D;D;D

Sift4G

Uncertain

0.055

T;D;T

Polyphen

0.40

B;P;B

Vest4

0.83

MutPred

0.40

Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);

MVP

0.92

MPC

1.7

ClinPred

0.97

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.43

gMVP

0.76

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over