rs2713579

Variant names:

• chr3-128479261-G-A
• rs2713579
• NM_001145661.2:c.*1758C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-128479261-G-A
• chr3-128479261-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001145661.2(GATA2):​c.*1758C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 151,892 control chromosomes in the GnomAD database, including 36,046 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.69 (36046 hom., cov: 31)
• Consequence: GATA2 NM_001145661.2 downstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.591
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-128479261-G-A is Benign according to our data. Variant chr3-128479261-G-A is described in ClinVar as Benign. ClinVar VariationId is 2203427.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA2	NM_001145661.2	c.*1758C>T		downstream_gene_variant		ENST00000487848.6	NP_001139133.1
GATA2	NM_032638.5	c.*1758C>T		downstream_gene_variant		ENST00000341105.7	NP_116027.2
GATA2	NM_001145662.1	c.*1758C>T		downstream_gene_variant			NP_001139134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7	c.*1758C>T		downstream_gene_variant		1	NM_032638.5	ENSP00000345681.2
GATA2	ENST00000487848.6	c.*1758C>T		downstream_gene_variant		1	NM_001145661.2	ENSP00000417074.1
GATA2	ENST00000696466.1	c.*1758C>T		downstream_gene_variant				ENSP00000512647.1
GATA2	ENST00000696672.1	c.*1597C>T		downstream_gene_variant				ENSP00000512796.1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104111 AN: 151774 Hom.: 36004 Cov.: 31

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.686 AC: 104212 AN: 151892 Hom.: 36046 Cov.: 31 AF XY: 0.683 AC XY: 50670 AN XY: 74186

African (AFR) AF: 0.757 AC: 31360 AN: 41416

American (AMR) AF: 0.702 AC: 10723 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2301 AN: 3470

East Asian (EAS) AF: 0.683 AC: 3510 AN: 5136

South Asian (SAS) AF: 0.637 AC: 3065 AN: 4814

European-Finnish (FIN) AF: 0.604 AC: 6365 AN: 10534

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.656 AC: 44538 AN: 67926

Other (OTH) AF: 0.681 AC: 1438 AN: 2112

Alfa AF: 0.657 Hom.: 14380

Bravo AF: 0.698

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Feb 11, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.36
DANN	Benign	0.39
PhyloP100		-0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2713579; hg19: chr3-128198104;