3-128481866-CGTTGGCGTTTCG-C

Position:

• chr3-128481866-CGTTGGCGTTTCG-C

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1 PM2 PM4 PP3 PP5_Moderate

The NM_032638.5(GATA2):​c.1084_1095delCGAAACGCCAAC​(p.Arg362_Asn365del) variant causes a conservative inframe deletion 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 NM_032638.5 conservative_inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 7.95

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 9 ACMG points.

• PM1: In a zinc_finger_region GATA-type 2 (size 24) in uniprot entity GATA2_HUMAN there are 6 pathogenic changes around while only 0 benign (100%) in NM_032638.5
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_032638.5.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 3-128481866-CGTTGGCGTTTCG-C is Pathogenic according to our data. Variant chr3-128481866-CGTTGGCGTTTCG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 29713.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-128481866-CGTTGGCGTTTCG-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA2	NM_032638.5	c.1084_1095delCGAAACGCCAAC	p.Arg362_Asn365del	conservative_inframe_deletion	5/6	ENST00000341105.7	NP_116027.2
GATA2	NM_001145661.2	c.1084_1095delCGAAACGCCAAC	p.Arg362_Asn365del	conservative_inframe_deletion	6/7		NP_001139133.1
GATA2	NM_001145662.1	c.1042_1053delCGAAACGCCAAC	p.Arg348_Asn351del	conservative_inframe_deletion	5/6		NP_001139134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7	c.1084_1095delCGAAACGCCAAC	p.Arg362_Asn365del	conservative_inframe_deletion	5/6	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: 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

Sep 08, 2011

- -

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

PS4_Supporting, PM2, PM4_Strong -

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: rs869320734; hg19: chr3-128200709;