rs1060500084

Positions:

• chr3-128486298-CC-AA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032638.5(GATA2):​c.299_300delinsTT​(p.Gly100Val) variant causes a missense 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G100E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GATA2 NM_032638.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3 O:1
• Conservation: PhyloP100: 1.88

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA2	NM_001145661.2	c.299_300delinsTT	p.Gly100Val	missense_variant	4/7	ENST00000487848.6
GATA2	NM_032638.5	c.299_300delinsTT	p.Gly100Val	missense_variant	3/6	ENST00000341105.7
GATA2	NM_001145662.1	c.299_300delinsTT	p.Gly100Val	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA2	ENST00000341105.7	c.299_300delinsTT	p.Gly100Val	missense_variant	3/6	1	NM_032638.5	P1
GATA2	ENST00000487848.6	c.299_300delinsTT	p.Gly100Val	missense_variant	4/7	1	NM_001145661.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Uncertain significance, criteria provided, single submitter	clinical testing	Invitae	Sep 10, 2023	ClinVar contains an entry for this variant (Variation ID: 404071). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 100 of the GATA2 protein (p.Gly100Val). This variant is present in population databases (no rsID available, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with GATA2-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. -
not provided, no classification provided	phenotyping only	GenomeConnect - Invitae Patient Insights Network	-	Variant interpreted as Uncertain significance and reported on 08-07-2020 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. -

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 19, 2015

- -

GATA2-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 10, 2023

The GATA2 c.299_300delinsTT variant is predicted to result in an in-frame deletion and insertion. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

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: rs1060500084; hg19: chr3-128205141;