rs869320770

chr3-128481937-GCGGC-Gchr3-128481937-GCGGC-GCGGCCGGC

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PP5_Moderate

The NM_032638.5(GATA2):c.1021_1024del(p.Ala341ProfsTer45) variant causes a frameshift change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. A341A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GATA2 NM_032638.5 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.91

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 Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 91 pathogenic variants in the truncated region.
• PP5: Variant 3-128481937-GCGGC-G is Pathogenic according to our data. Variant chr3-128481937-GCGGC-G is described in ClinVar as [Pathogenic]. Clinvar id is 1184187.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-128481937-GCGGC-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA2	NM_001145661.2	c.1021_1024del	p.Ala341ProfsTer45	frameshift_variant	6/7	ENST00000487848.6
GATA2	NM_032638.5	c.1021_1024del	p.Ala341ProfsTer45	frameshift_variant	5/6	ENST00000341105.7
GATA2	NM_001145662.1	c.1018-39_1018-36del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA2	ENST00000341105.7	c.1021_1024del	p.Ala341ProfsTer45	frameshift_variant	5/6	1	NM_032638.5	P1
GATA2	ENST00000487848.6	c.1021_1024del	p.Ala341ProfsTer45	frameshift_variant	6/7	1	NM_001145661.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Deafness-lymphedema-leukemia syndrome;CN300066:GATA2 deficiency with susceptibility to MDS/AML Pathogenic:1

Pathogenic, criteria provided, single submitter

curation

Molecular Pathology Research Laboratory, SA Pathology

Jul 06, 2021

PVS1, PS4_Supporting, PM2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-128200780;