rs863224874

Positions:

• chr3-128481836-A-AGAGG

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_032638.5(GATA2):​c.1122_1125dupCCTC​(p.Tyr376fs) 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 (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GATA2 NM_032638.5 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 0.672

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 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 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 4 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-128481836-A-AGAGG is Pathogenic according to our data. Variant chr3-128481836-A-AGAGG is described in ClinVar as [Pathogenic]. Clinvar id is 216932.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA2	NM_032638.5	c.1122_1125dupCCTC	p.Tyr376fs	frameshift_variant	5/6	ENST00000341105.7	NP_116027.2
GATA2	NM_001145661.2	c.1122_1125dupCCTC	p.Tyr376fs	frameshift_variant	6/7		NP_001139133.1
GATA2	NM_001145662.1	c.1080_1083dupCCTC	p.Tyr362fs	frameshift_variant	5/6		NP_001139134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7	c.1122_1125dupCCTC	p.Tyr376fs	frameshift_variant	5/6	1	NM_032638.5	ENSP00000345681.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Deafness-lymphedema-leukemia syndrome Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

UCLA Clinical Genomics Center, UCLA

Aug 26, 2014

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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: rs863224874; hg19: chr3-128200679;