rs1553770444
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM4PP3
The NM_032638.5(GATA2):c.1160_1168del(p.Thr387_Lys389del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T387T) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Consequence
GATA2
NM_032638.5 inframe_deletion
NM_032638.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.94
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM1
?
In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 6 uncertain in NM_032638.5
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
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA2 | NM_001145661.2 | c.1160_1168del | p.Thr387_Lys389del | inframe_deletion | 7/7 | ENST00000487848.6 | |
GATA2 | NM_032638.5 | c.1160_1168del | p.Thr387_Lys389del | inframe_deletion | 6/6 | ENST00000341105.7 | |
GATA2 | NM_001145662.1 | c.1118_1126del | p.Thr373_Lys375del | inframe_deletion | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA2 | ENST00000341105.7 | c.1160_1168del | p.Thr387_Lys389del | inframe_deletion | 6/6 | 1 | NM_032638.5 | P1 | |
GATA2 | ENST00000487848.6 | c.1160_1168del | p.Thr387_Lys389del | inframe_deletion | 7/7 | 1 | NM_001145661.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Monocytopenia with susceptibility to infections Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 26, 2024 | - - |
Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 23, 2017 | This variant, c.1160_1168delCCATGAAGA, results in the deletion of 3 amino acids of the GATA2 protein (p.Thr387_Lys389del), but otherwise preserves the integrity of the reading frame. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids 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. This variant has not been reported in the literature in individuals with GATA2-related disease. This variant is not present in population databases (ExAC no frequency). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at