rs587778378

Positions:

chr3-128485811-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

The ENST00000341105.7(GATA2):c.787G>A(p.Gly263Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,790 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G263A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GATA2
ENST00000341105.7 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1O:1

Conservation

PhyloP100: 1.43

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 3-128485811-C-T is Benign according to our data. Variant chr3-128485811-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 134468.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2, not_provided=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GATA2	NM_001145661.2 linkuse as main transcript	c.787G>A	p.Gly263Arg	missense_variant	4/7	ENST00000487848.6	NP_001139133.1
GATA2	NM_032638.5 linkuse as main transcript	c.787G>A	p.Gly263Arg	missense_variant	3/6	ENST00000341105.7	NP_116027.2
GATA2	NM_001145662.1 linkuse as main transcript	c.787G>A	p.Gly263Arg	missense_variant	3/6		NP_001139134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7 linkuse as main transcript	c.787G>A	p.Gly263Arg	missense_variant	3/6	1	NM_032638.5	ENSP00000345681	P1	P23769-1
GATA2	ENST00000487848.6 linkuse as main transcript	c.787G>A	p.Gly263Arg	missense_variant	4/7	1	NM_001145661.2	ENSP00000417074	P1	P23769-1
GATA2	ENST00000430265.6 linkuse as main transcript	c.787G>A	p.Gly263Arg	missense_variant	3/6	1		ENSP00000400259		P23769-2
GATA2	ENST00000696466.1 linkuse as main transcript	c.1069G>A	p.Gly357Arg	missense_variant	5/8			ENSP00000512647

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461664

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1Other:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

GATA2-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 07, 2023

The GATA2 c.787G>A variant is predicted to result in the amino acid substitution p.Gly263Arg. To our knowledge, this variant has not been reported in the literature in association with disease. This variant has been reported in a study of cancer-susceptibility genes in a healthy, ancestrally diverse cohort (Table S1, Bodian et al. 2014. PubMed ID: 24728327) and is reported in 0.011% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-128204654-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Acute myeloid leukemia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Nov 29, 2023

- -

Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 19, 2023

- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.80

D;.;D

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.97

.;D;D

M_CAP

Pathogenic

0.31

MetaRNN

Uncertain

0.49

T;T;T

MetaSVM

Uncertain

0.35

MutationAssessor

Benign

1.4

L;L;L

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Uncertain

0.45

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.041

D;D;D

Polyphen

0.79

P;P;P

Vest4

0.68

MutPred

0.29

Gain of glycosylation at Y260 (P = 0.0107);Gain of glycosylation at Y260 (P = 0.0107);Gain of glycosylation at Y260 (P = 0.0107);

MVP

0.83

MPC

0.75

ClinPred

0.89

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.19

gMVP

0.57

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over