rs34172218

Positions:

chr3-128481229-C-T

Variant summary

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

The NM_032638.5(GATA2):c.1233G>A(p.Ala411=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 1,614,210 control chromosomes in the GnomAD database, including 552 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 60 hom., cov: 33)

Exomes 𝑓: 0.023 ( 492 hom. )

Consequence

GATA2
NM_032638.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -7.51

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=-0.61).

BP6

Variant 3-128481229-C-T is Benign according to our data. Variant chr3-128481229-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 257562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-128481229-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-7.51 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GATA2	NM_001145661.2 linkuse as main transcript	c.1233G>A	p.Ala411=	synonymous_variant	7/7	ENST00000487848.6
GATA2	NM_032638.5 linkuse as main transcript	c.1233G>A	p.Ala411=	synonymous_variant	6/6	ENST00000341105.7
GATA2	NM_001145662.1 linkuse as main transcript	c.1191G>A	p.Ala397=	synonymous_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA2	ENST00000341105.7 linkuse as main transcript	c.1233G>A	p.Ala411=	synonymous_variant	6/6	1	NM_032638.5	P1	P23769-1
GATA2	ENST00000487848.6 linkuse as main transcript	c.1233G>A	p.Ala411=	synonymous_variant	7/7	1	NM_001145661.2	P1	P23769-1

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2870

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00490

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.0216

Gnomad ASJ

AF:

0.0585

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.0186

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0260

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0220

AC:

5542

AN:

251474

Hom.:

AF XY:

0.0223

AC XY:

3037

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00431

Gnomad AMR exome

AF:

0.0195

Gnomad ASJ exome

AF:

0.0608

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00601

Gnomad FIN exome

AF:

0.0181

Gnomad NFE exome

AF:

0.0300

Gnomad OTH exome

AF:

0.0323

GnomAD4 exome

AF:

0.0228

AC:

33262

AN:

1461890

Hom.:

492

Cov.:

AF XY:

0.0226

AC XY:

16463

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00436

Gnomad4 AMR exome

AF:

0.0206

Gnomad4 ASJ exome

AF:

0.0596

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.00660

Gnomad4 FIN exome

AF:

0.0192

Gnomad4 NFE exome

AF:

0.0245

Gnomad4 OTH exome

AF:

0.0242

GnomAD4 genome

AF:

0.0188

AC:

2871

AN:

152320

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1374

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00488

Gnomad4 AMR

AF:

0.0216

Gnomad4 ASJ

AF:

0.0585

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00642

Gnomad4 FIN

AF:

0.0186

Gnomad4 NFE

AF:

0.0260

Gnomad4 OTH

AF:

0.0294

Alfa

AF:

0.0260

Hom.:

Bravo

AF:

0.0195

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0324

EpiControl

AF:

0.0341

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	Mar 22, 2018	- -
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, silent variant not in splice consensus -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 13, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 18, 2020	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Deafness-lymphedema-leukemia syndrome

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.84

DANN

Benign

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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