3-128481616-T-C

Variant names:

• chr3-128481616-T-C
• rs2713604
• NM_001145661.2:c.1143+203A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001145661.2(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_001145661.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.110
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• deafness-lymphedema-leukemia syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• GATA2 deficiency with susceptibility to MDS/AML

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• monocytopenia with susceptibility to infections

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
• acute myeloid leukemia

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• myelodysplastic syndrome

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145661.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA2	NM_001145661.2	MANE Plus Clinical	c.1143+203A>G		intron	N/A	NP_001139133.1
	GATA2	NM_032638.5	MANE Select	c.1143+203A>G		intron	N/A	NP_116027.2
	GATA2	NM_001145662.1		c.1101+203A>G		intron	N/A	NP_001139134.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA2	ENST00000341105.7	TSL:1 MANE Select	c.1143+203A>G		intron	N/A	ENSP00000345681.2
	GATA2	ENST00000487848.6	TSL:1 MANE Plus Clinical	c.1143+203A>G		intron	N/A	ENSP00000417074.1
	GATA2	ENST00000430265.6	TSL:1	c.1101+203A>G		intron	N/A	ENSP00000400259.2

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

African (AFR) AF: 0.760 AC: 31447 AN: 41404

American (AMR) AF: 0.705 AC: 10763 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2426 AN: 3472

East Asian (EAS) AF: 0.693 AC: 3549 AN: 5122

South Asian (SAS) AF: 0.604 AC: 2901 AN: 4800

European-Finnish (FIN) AF: 0.625 AC: 6564 AN: 10502

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.665 AC: 45143 AN: 67900

Other (OTH) AF: 0.698 AC: 1471 AN: 2108

Alfa AF: 0.678 Hom.: 116254

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Sep 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.99
DANN	Benign	0.46
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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