rs1553770655

Positions:

• chr3-128483319-AGGCTGCAGATGTCCGGATAGGAAACTCC-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3 PP5_Moderate

The ENST00000341105.7(GATA2):​c.1017+513_1017+540del variant causes a intron 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 Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GATA2 ENST00000341105.7 intron
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 8.53

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 5 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
• PP5: Variant 3-128483319-AGGCTGCAGATGTCCGGATAGGAAACTCC-A is Pathogenic according to our data. Variant chr3-128483319-AGGCTGCAGATGTCCGGATAGGAAACTCC-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 39587.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_001145661.2	c.1017+513_1017+540del		intron_variant		ENST00000487848.6	NP_001139133.1
GATA2	NM_032638.5	c.1017+513_1017+540del		intron_variant		ENST00000341105.7	NP_116027.2
GATA2	NM_001145662.1	c.1017+513_1017+540del		intron_variant			NP_001139134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7	c.1017+513_1017+540del		intron_variant		1	NM_032638.5	ENSP00000345681	P1
GATA2	ENST00000487848.6	c.1017+513_1017+540del		intron_variant		1	NM_001145661.2	ENSP00000417074	P1
GATA2	ENST00000430265.6	c.1017+513_1017+540del		intron_variant		1		ENSP00000400259
GATA2	ENST00000696466.1	c.1299+513_1299+540del		intron_variant				ENSP00000512647

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: Likely 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

Oct 01, 2012

- -

Deafness-lymphedema-leukemia syndrome;CN300066:GATA2 deficiency with susceptibility to MDS/AML Pathogenic:1

Likely pathogenic, criteria provided, single submitter

curation

Molecular Pathology Research Laboratory, SA Pathology

Jul 06, 2021

PS3_Supporting, PS4_Moderate, PM1, 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: rs1553770655; hg19: chr3-128202162;