3-128485850-G-C

Position:

chr3-128485850-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000341105.7(GATA2):c.748C>G(p.Pro250Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00173 in 1,614,048 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P250S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0022 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 49 hom. )

Consequence

GATA2
ENST00000341105.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 4.92

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008040041).

BP6

Variant 3-128485850-G-C is Benign according to our data. Variant chr3-128485850-G-C is described in ClinVar as [Benign]. Clinvar id is 134466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-128485850-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00223 (339/152302) while in subpopulation EAS AF= 0.0524 (271/5170). AF 95% confidence interval is 0.0473. There are 11 homozygotes in gnomad4. There are 170 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 339 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GATA2	NM_001145661.2 linkuse as main transcript	c.748C>G	p.Pro250Ala	missense_variant	4/7	ENST00000487848.6	NP_001139133.1
GATA2	NM_032638.5 linkuse as main transcript	c.748C>G	p.Pro250Ala	missense_variant	3/6	ENST00000341105.7	NP_116027.2
GATA2	NM_001145662.1 linkuse as main transcript	c.748C>G	p.Pro250Ala	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.748C>G	p.Pro250Ala	missense_variant	3/6	1	NM_032638.5	ENSP00000345681	P1	P23769-1
GATA2	ENST00000487848.6 linkuse as main transcript	c.748C>G	p.Pro250Ala	missense_variant	4/7	1	NM_001145661.2	ENSP00000417074	P1	P23769-1
GATA2	ENST00000430265.6 linkuse as main transcript	c.748C>G	p.Pro250Ala	missense_variant	3/6	1		ENSP00000400259		P23769-2
GATA2	ENST00000696466.1 linkuse as main transcript	c.1030C>G	p.Pro344Ala	missense_variant	5/8			ENSP00000512647

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

342

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0527

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00500

AC:

1252

AN:

250380

Hom.:

AF XY:

0.00445

AC XY:

603

AN XY:

135536

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.00836

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0503

Gnomad SAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000885

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00167

AC:

2447

AN:

1461746

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

1199

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00760

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0470

Gnomad4 SAS exome

AF:

0.00105

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000423

Gnomad4 OTH exome

AF:

0.00164

GnomAD4 genome

AF:

0.00223

AC:

339

AN:

152302

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

170

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0524

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00191

Hom.:

Bravo

AF:

0.00266

ExAC

AF:

0.00464

AC:

563

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Aug 23, 2017	- -
not provided, no classification provided	reference population	ITMI	Sep 19, 2013	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Deafness-lymphedema-leukemia syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.82

D;.;D

Eigen

Benign

0.092

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

.;D;D

MetaRNN

Benign

0.0080

T;T;T

MetaSVM

Uncertain

0.29

MutationAssessor

Benign

1.4

L;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-4.1

D;D;D

REVEL

Uncertain

0.53

Sift

Benign

0.066

T;T;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.021

B;B;B

Vest4

0.35

MVP

0.80

MPC

1.4

ClinPred

0.036

GERP RS

4.6

Varity_R

0.26

gMVP

0.62

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