rs1553770655

Variant names:

• chr3-128483319-AGGCTGCAGATGTCCGGATAGGAAACTCC-A
• rs1553770655
• NM_001145661.2:c.1017+513_1017+540delGGAGTTTCCTATCCGGACATCTGCAGCC

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PP3 PP5_Moderate

The NM_001145661.2(GATA2):​c.1017+513_1017+540delGGAGTTTCCTATCCGGACATCTGCAGCC variant causes a intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GATA2 NM_001145661.2 intron
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 8.53
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• deafness-lymphedema-leukemia syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• GATA2 deficiency with susceptibility to MDS/AML

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• monocytopenia with susceptibility to infections

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
• acute myeloid leukemia

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• myelodysplastic syndrome

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• 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 VariationId is 39587.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA2	NM_001145661.2	c.1017+513_1017+540delGGAGTTTCCTATCCGGACATCTGCAGCC		intron_variant	Intron 5 of 6	ENST00000487848.6	NP_001139133.1
GATA2	NM_032638.5	c.1017+513_1017+540delGGAGTTTCCTATCCGGACATCTGCAGCC		intron_variant	Intron 4 of 5	ENST00000341105.7	NP_116027.2
GATA2	NM_001145662.1	c.1017+513_1017+540delGGAGTTTCCTATCCGGACATCTGCAGCC		intron_variant	Intron 4 of 5		NP_001139134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7	c.1017+513_1017+540delGGAGTTTCCTATCCGGACATCTGCAGCC		intron_variant	Intron 4 of 5	1	NM_032638.5	ENSP00000345681.2
GATA2	ENST00000487848.6	c.1017+513_1017+540delGGAGTTTCCTATCCGGACATCTGCAGCC		intron_variant	Intron 5 of 6	1	NM_001145661.2	ENSP00000417074.1
GATA2	ENST00000430265.6	c.1017+513_1017+540delGGAGTTTCCTATCCGGACATCTGCAGCC		intron_variant	Intron 4 of 5	1		ENSP00000400259.2
GATA2	ENST00000696466.1	c.1299+513_1299+540delGGAGTTTCCTATCCGGACATCTGCAGCC		intron_variant	Intron 6 of 7			ENSP00000512647.1

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

Oct 01, 2012

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

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

Jul 06, 2021

Molecular Pathology Research Laboratory, SA Pathology

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: curation

PS3_Supporting, PS4_Moderate, PM1, PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.5
Mutation Taster		=6/94	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1553770655; hg19: chr3-128202162;