rs1553770524

Positions:

• chr3-128481939-GGCCG-AAGGC

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032638.5(GATA2):​c.1019_1023delCGGCCinsGCCTT​(p.SerAla340CysLeu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GATA2 NM_032638.5 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U: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]

GATA2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA2	NM_032638.5	c.1019_1023delCGGCCinsGCCTT	p.SerAla340CysLeu	missense_variant, splice_region_variant		ENST00000341105.7	NP_116027.2
GATA2	NM_001145661.2	c.1019_1023delCGGCCinsGCCTT	p.SerAla340CysLeu	missense_variant, splice_region_variant			NP_001139133.1
GATA2	NM_001145662.1	c.1018-41_1018-37delCGGCCinsGCCTT		intron_variant			NP_001139134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7	c.1019_1023delCGGCCinsGCCTT	p.SerAla340CysLeu	missense_variant, splice_region_variant		1	NM_032638.5	ENSP00000345681.2

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: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 13, 2017

This variant is not present in population databases (ExAC no frequency). This variant, c.1019_1023delinsGCCTT, replaces serine with cysteine at codon 340 of the GATA2 protein and replaces alanine with leucine at codon 341 of the GATA2 protein (p.Ser340_Ala341delinsCysLeu). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and cysteine. The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and leucine. This variant has not been reported in the literature in individuals with a GATA2-related disease. In summary, this variant has uncertain impact on GATA2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of the p.Ser340Cys missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15") or the p.Ala341Leu missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). -

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: rs1553770524; hg19: chr3-128200782;