3-128487017-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032638.5(GATA2):c.15C>G(p.Pro5=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 1,589,600 control chromosomes in the GnomAD database, including 326,671 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. P5P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.68 ( 35936 hom., cov: 35)

Exomes 𝑓: 0.63 ( 290735 hom. )

Consequence

GATA2
NM_032638.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15O:1

Conservation

PhyloP100: -5.44

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 3-128487017-G-C is Benign according to our data. Variant chr3-128487017-G-C is described in ClinVar as [Benign]. Clinvar id is 257563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-128487017-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-5.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GATA2	NM_001145661.2 linkuse as main transcript	c.15C>G	p.Pro5=	synonymous_variant	3/7	ENST00000487848.6
GATA2	NM_032638.5 linkuse as main transcript	c.15C>G	p.Pro5=	synonymous_variant	2/6	ENST00000341105.7
GATA2	NM_001145662.1 linkuse as main transcript	c.15C>G	p.Pro5=	synonymous_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA2	ENST00000341105.7 linkuse as main transcript	c.15C>G	p.Pro5=	synonymous_variant	2/6	1	NM_032638.5	P1	P23769-1
GATA2	ENST00000487848.6 linkuse as main transcript	c.15C>G	p.Pro5=	synonymous_variant	3/7	1	NM_001145661.2	P1	P23769-1

Frequencies

GnomAD3 genomes

AF:

0.681

AC:

103585

AN:

152070

Hom.:

35892

Cov.:

show subpopulations

Gnomad AFR

AF:

0.786

Gnomad AMI

AF:

0.763

Gnomad AMR

AF:

0.718

Gnomad ASJ

AF:

0.732

Gnomad EAS

AF:

0.703

Gnomad SAS

AF:

0.656

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.777

Gnomad NFE

AF:

0.628

Gnomad OTH

AF:

0.691

GnomAD3 exomes

AF:

0.665

AC:

137413

AN:

206734

Hom.:

45821

AF XY:

0.662

AC XY:

74294

AN XY:

112160

show subpopulations

Gnomad AFR exome

AF:

0.786

Gnomad AMR exome

AF:

0.709

Gnomad ASJ exome

AF:

0.752

Gnomad EAS exome

AF:

0.709

Gnomad SAS exome

AF:

0.673

Gnomad FIN exome

AF:

0.533

Gnomad NFE exome

AF:

0.638

Gnomad OTH exome

AF:

0.678

GnomAD4 exome

AF:

0.634

AC:

911208

AN:

1437412

Hom.:

290735

Cov.:

AF XY:

0.635

AC XY:

452850

AN XY:

712660

show subpopulations

Gnomad4 AFR exome

AF:

0.793

Gnomad4 AMR exome

AF:

0.712

Gnomad4 ASJ exome

AF:

0.752

Gnomad4 EAS exome

AF:

0.641

Gnomad4 SAS exome

AF:

0.673

Gnomad4 FIN exome

AF:

0.538

Gnomad4 NFE exome

AF:

0.622

Gnomad4 OTH exome

AF:

0.661

GnomAD4 genome

AF:

0.681

AC:

103686

AN:

152188

Hom.:

35936

Cov.:

AF XY:

0.677

AC XY:

50405

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.786

Gnomad4 AMR

AF:

0.718

Gnomad4 ASJ

AF:

0.732

Gnomad4 EAS

AF:

0.702

Gnomad4 SAS

AF:

0.656

Gnomad4 FIN

AF:

0.531

Gnomad4 NFE

AF:

0.628

Gnomad4 OTH

AF:

0.692

Alfa

AF:

0.652

Hom.:

9943

Bravo

AF:

0.702

Asia WGS

AF:

0.671

AC:

2330

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:15Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:9

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Apr 04, 2018	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
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 88% of patients studied by a panel of primary immunodeficiencies. Number of patients: 84. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 14, 2018	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 16, 2023	- -

Deafness-lymphedema-leukemia syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

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

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

Cadd

Benign

2.4

Dann

Benign

0.85

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