rs1553770955

chr3-128485966-A-ACGC

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_032638.5(GATA2):c.631_632insGCG(p.Gly210dup) variant causes a inframe insertion 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V211V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GATA2 NM_032638.5 inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.257

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_032638.5. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA2	NM_001145661.2	c.631_632insGCG	p.Gly210dup	inframe_insertion	4/7	ENST00000487848.6
GATA2	NM_032638.5	c.631_632insGCG	p.Gly210dup	inframe_insertion	3/6	ENST00000341105.7
GATA2	NM_001145662.1	c.631_632insGCG	p.Gly210dup	inframe_insertion	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA2	ENST00000341105.7	c.631_632insGCG	p.Gly210dup	inframe_insertion	3/6	1	NM_032638.5	P1
GATA2	ENST00000487848.6	c.631_632insGCG	p.Gly210dup	inframe_insertion	4/7	1	NM_001145661.2	P1
GATA2	ENST00000430265.6	c.631_632insGCG	p.Gly210dup	inframe_insertion	3/6	1
GATA2	ENST00000696466.1	c.913_914insGCG	p.Gly304dup	inframe_insertion	5/8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Invitae

Jul 03, 2023

This variant is not present in population databases (gnomAD no frequency). This variant, c.629_631dup, results in the insertion of 1 amino acid(s) of the GATA2 protein (p.Gly210dup), but otherwise preserves the integrity of the reading frame. This variant has not been reported in the literature in individuals affected with GATA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 539722). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

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: rs1553770955; hg19: chr3-128204809;