rs869320735

Positions:

• chr3-128486354-CT-CGC

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_032638.5(GATA2):​c.243delinsGC​(p.Gly82ArgfsTer103) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GATA2 NM_032638.5 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 1.06

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 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-128486355-T-GC is Pathogenic according to our data. Variant chr3-128486355-T-GC is described in ClinVar as [Pathogenic]. Clinvar id is 29714.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA2	NM_001145661.2	c.243delinsGC	p.Gly82ArgfsTer103	frameshift_variant	4/7	ENST00000487848.6
GATA2	NM_032638.5	c.243delinsGC	p.Gly82ArgfsTer103	frameshift_variant	3/6	ENST00000341105.7
GATA2	NM_001145662.1	c.243delinsGC	p.Gly82ArgfsTer103	frameshift_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA2	ENST00000341105.7	c.243delinsGC	p.Gly82ArgfsTer103	frameshift_variant	3/6	1	NM_032638.5	P1
GATA2	ENST00000487848.6	c.243delinsGC	p.Gly82ArgfsTer103	frameshift_variant	4/7	1	NM_001145661.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Monocytopenia with susceptibility to infections Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 08, 2011

- -

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs869320735; hg19: chr3-128205198;