rs34870876

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_032638.5(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 (★★).

Frequency

Genomes: 𝑓 0.040 ( 179 hom., cov: 32)

Exomes 𝑓: 0.054 ( 2541 hom. )

Consequence

GATA2
NM_032638.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.77

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=-0.75).

BP6

Variant 3-128486034-C-G is Benign according to our data. Variant chr3-128486034-C-G is described in ClinVar as [Benign]. Clinvar id is 257566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-128486034-C-G is described in Lovd as [Benign]. Variant chr3-128486034-C-G is described in Lovd as [Likely_benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA2	NM_032638.5 link	c.564G>C	p.Thr188Thr	synonymous_variant	Exon 3 of 6	ENST00000341105.7	NP_116027.2	P23769-1
GATA2	NM_001145661.2 link	c.564G>C	p.Thr188Thr	synonymous_variant	Exon 4 of 7		NP_001139133.1	P23769-1
GATA2	NM_001145662.1 link	c.564G>C	p.Thr188Thr	synonymous_variant	Exon 3 of 6		NP_001139134.1	P23769-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7 link	c.564G>C	p.Thr188Thr	synonymous_variant	Exon 3 of 6	1	NM_032638.5	ENSP00000345681.2		P23769-1

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

GnomAD3 exomes

AF:

0.0408

AC:

10218

AN:

250610

Hom.:

320

AF XY:

0.0413

AC XY:

5599

AN XY:

135692

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 SAS exome

AF:

0.0240

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

Gnomad4 AFR exome

AF:

0.00791

Gnomad4 AMR exome

AF:

0.0150

Gnomad4 ASJ exome

AF:

0.0112

Gnomad4 EAS exome

AF:

0.000178

Gnomad4 SAS exome

AF:

0.0237

Gnomad4 FIN exome

AF:

0.0911

Gnomad4 NFE exome

AF:

0.0614

Gnomad4 OTH exome

AF:

0.0443

GnomAD4 genome

AF:

0.0396

AC:

6012

AN:

151820

Hom.:

179

Cov.:

AF XY:

0.0401

AC XY:

2977

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.0235

Gnomad4 ASJ

AF:

0.00811

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.0217

Gnomad4 FIN

AF:

0.0918

Gnomad4 NFE

AF:

0.0588

Gnomad4 OTH

AF:

0.0351

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

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 13, 2017

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 31, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:4

Nov 06, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Inborn genetic diseases

Benign:1

Nov 21, 2024

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

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

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Deafness-lymphedema-leukemia syndrome

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.022

DANN

Benign

0.60

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

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