rs11708606

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032638.5(GATA2):c.1018-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,611,562 control chromosomes in the GnomAD database, including 27,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2468 hom., cov: 33)

Exomes 𝑓: 0.18 ( 24947 hom. )

Consequence

GATA2
NM_032638.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.0490

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:

GATA2 (HGNC:):

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 (BayesDel_noAF=-0.54).

BP6

Variant 3-128481963-G-A is Benign according to our data. Variant chr3-128481963-G-A is described in ClinVar as [Benign]. Clinvar id is 257561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-128481963-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
GATA2	NM_032638.5 linkuse as main transcript	c.1018-19C>T	intron_variant	ENST00000341105.7	NP_116027.2	P23769-1
GATA2	NM_001145661.2 linkuse as main transcript	c.1018-19C>T	intron_variant		NP_001139133.1	P23769-1
GATA2	NM_001145662.1 linkuse as main transcript	c.1018-61C>T	intron_variant		NP_001139134.1	P23769-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7 linkuse as main transcript	c.1018-19C>T		intron_variant		1	NM_032638.5	ENSP00000345681.2		P23769-1

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26426

AN:

151922

Hom.:

2467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.173

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.0534

Gnomad SAS

AF:

0.0722

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.172

Gnomad NFE

AF:

0.194

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.156

AC:

38589

AN:

246728

Hom.:

3336

AF XY:

0.156

AC XY:

20902

AN XY:

134120

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.0538

Gnomad SAS exome

AF:

0.0827

Gnomad FIN exome

AF:

0.191

Gnomad NFE exome

AF:

0.198

Gnomad OTH exome

AF:

0.175

GnomAD4 exome

AF:

0.181

AC:

263459

AN:

1459522

Hom.:

24947

Cov.:

AF XY:

0.177

AC XY:

128671

AN XY:

726092

show subpopulations

Gnomad4 AFR exome

AF:

0.176

Gnomad4 AMR exome

AF:

0.124

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.0518

Gnomad4 SAS exome

AF:

0.0851

Gnomad4 FIN exome

AF:

0.191

Gnomad4 NFE exome

AF:

0.196

Gnomad4 OTH exome

AF:

0.174

GnomAD4 genome

AF:

0.174

AC:

26441

AN:

152040

Hom.:

2468

Cov.:

AF XY:

0.171

AC XY:

12692

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.173

Gnomad4 AMR

AF:

0.155

Gnomad4 ASJ

AF:

0.117

Gnomad4 EAS

AF:

0.0534

Gnomad4 SAS

AF:

0.0731

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.194

Gnomad4 OTH

AF:

0.176

Alfa

AF:

0.178

Hom.:

1038

Bravo

AF:

0.173

Asia WGS

AF:

0.0710

AC:

247

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Apr 03, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 31, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 06, 2023	- -

Monocytopenia with susceptibility to infections

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

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

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.9

DANN

Benign

0.92

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.1

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