3-128481616-T-C

Position:

• chr3-128481616-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032638.5(GATA2):​c.1143+203A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 151,788 control chromosomes in the GnomAD database, including 36,637 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.69 (36637 hom., cov: 31)
• Consequence: GATA2 NM_032638.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.110

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-128481616-T-C is Benign according to our data. Variant chr3-128481616-T-C is described in ClinVar as [Benign]. Clinvar id is 539725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA2	NM_001145661.2	c.1143+203A>G		intron_variant		ENST00000487848.6
GATA2	NM_032638.5	c.1143+203A>G		intron_variant		ENST00000341105.7
GATA2	NM_001145662.1	c.1101+203A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA2	ENST00000341105.7	c.1143+203A>G		intron_variant		1	NM_032638.5	P1
GATA2	ENST00000487848.6	c.1143+203A>G		intron_variant		1	NM_001145661.2	P1

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105137 AN: 151672 Hom.: 36594 Cov.: 31

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.832

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.697

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.693 AC: 105238 AN: 151788 Hom.: 36637 Cov.: 31 AF XY: 0.690 AC XY: 51219 AN XY: 74180

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.698

Alfa AF: 0.673 Hom.: 71145

Bravo AF: 0.704

Asia WGS AF: 0.641 AC: 2228 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 14, 2018

This variant is associated with the following publications: (PMID: 16934006) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.99
DANN	Benign	0.46

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

Other links and lift over

dbSNP: rs2713604; hg19: chr3-128200459; COSMIC: COSV62007148; COSMIC: COSV62007148;