Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001145661.2(GATA2):c.564G>C(p.Thr188Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0527 in 1,605,602 control chromosomes in the GnomAD database, including 2,720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T188T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.040 ( 179 hom., cov: 32)

Exomes 𝑓: 0.054 ( 2541 hom. )

Consequence

GATA2
NM_001145661.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -2.77

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

deafness-lymphedema-leukemia syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
GATA2 deficiency with susceptibility to MDS/AML
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
monocytopenia with susceptibility to infections
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
acute myeloid leukemia
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
myelodysplastic syndrome
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

GATA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 3-128486034-C-G is Benign according to our data. Variant chr3-128486034-C-G is described in ClinVar as Benign. ClinVar VariationId is 257566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.77 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145661.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GATA2	NM_001145661.2	MANE Plus Clinical	c.564G>C	p.Thr188Thr	synonymous	Exon 4 of 7	NP_001139133.1
GATA2	NM_032638.5	MANE Select	c.564G>C	p.Thr188Thr	synonymous	Exon 3 of 6	NP_116027.2
GATA2	NM_001145662.1		c.564G>C	p.Thr188Thr	synonymous	Exon 3 of 6	NP_001139134.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
GATA2	ENST00000341105.7	TSL:1 MANE Select	c.564G>C	p.Thr188Thr	synonymous	Exon 3 of 6	ENSP00000345681.2
GATA2	ENST00000487848.6	TSL:1 MANE Plus Clinical	c.564G>C	p.Thr188Thr	synonymous	Exon 4 of 7	ENSP00000417074.1
GATA2	ENST00000430265.6	TSL:1	c.564G>C	p.Thr188Thr	synonymous	Exon 3 of 6	ENSP00000400259.2

Frequencies

GnomAD3 genomes

AF:

0.0396

AC:

6013

AN:

151698

Hom.:

179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.0796

Gnomad AMR

AF:

0.0236

Gnomad ASJ

AF:

0.00811

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0217

Gnomad FIN

AF:

0.0918

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0588

Gnomad OTH

AF:

0.0355

GnomAD2 exomes

AF:

0.0408

AC:

10218

AN:

250610

AF XY:

0.0413

show subpopulations

Gnomad AFR exome

AF:

0.0104

Gnomad AMR exome

AF:

0.0140

Gnomad ASJ exome

AF:

0.0107

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.0881

Gnomad NFE exome

AF:

0.0582

Gnomad OTH exome

AF:

0.0388

GnomAD4 exome

AF:

0.0541

AC:

78645

AN:

1453782

Hom.:

2541

Cov.:

AF XY:

0.0529

AC XY:

38285

AN XY:

723156

show subpopulations

African (AFR)

AF:

0.00791

AC:

263

AN:

33242

American (AMR)

AF:

0.0150

AC:

668

AN:

44494

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

289

AN:

25836

East Asian (EAS)

AF:

0.000178

AC:

AN:

39228

South Asian (SAS)

AF:

0.0237

AC:

2040

AN:

86194

European-Finnish (FIN)

AF:

0.0911

AC:

4701

AN:

51620

Middle Eastern (MID)

AF:

0.00663

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.0614

AC:

67989

AN:

1107604

Other (OTH)

AF:

0.0443

AC:

2650

AN:

59836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

4848

9696

14543

19391

24239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2496

4992

7488

9984

12480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0396

AC:

6012

AN:

151820

Hom.:

179

Cov.:

AF XY:

0.0401

AC XY:

2977

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.0101

AC:

417

AN:

41472

American (AMR)

AF:

0.0235

AC:

358

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00811

AC:

AN:

3452

East Asian (EAS)

AF:

0.000195

AC:

AN:

5140

South Asian (SAS)

AF:

0.0217

AC:

104

AN:

4784

European-Finnish (FIN)

AF:

0.0918

AC:

963

AN:

10492

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0588

AC:

3993

AN:

67910

Other (OTH)

AF:

0.0351

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

285

570

854

1139

1424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0370

Hom.:

Bravo

AF:

0.0327

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.0481

EpiControl

AF:

0.0482

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (4)

Deafness-lymphedema-leukemia syndrome (1)

Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.022

(source)

DANN

Benign

0.60

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs34870876

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over