rs1553770978
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_032638.5(GATA2):c.526A>C(p.Thr176Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T176K) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Consequence
GATA2
NM_032638.5 missense
NM_032638.5 missense
Scores
9
8
1
Clinical Significance
Conservation
PhyloP100: 4.69
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 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 3-128486072-T-G is Pathogenic according to our data. Variant chr3-128486072-T-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 430908.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA2 | NM_001145661.2 | c.526A>C | p.Thr176Pro | missense_variant | 4/7 | ENST00000487848.6 | |
GATA2 | NM_032638.5 | c.526A>C | p.Thr176Pro | missense_variant | 3/6 | ENST00000341105.7 | |
GATA2 | NM_001145662.1 | c.526A>C | p.Thr176Pro | missense_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA2 | ENST00000341105.7 | c.526A>C | p.Thr176Pro | missense_variant | 3/6 | 1 | NM_032638.5 | P1 | |
GATA2 | ENST00000487848.6 | c.526A>C | p.Thr176Pro | missense_variant | 4/7 | 1 | NM_001145661.2 | P1 | |
GATA2 | ENST00000430265.6 | c.526A>C | p.Thr176Pro | missense_variant | 3/6 | 1 | |||
GATA2 | ENST00000696466.1 | c.808A>C | p.Thr270Pro | missense_variant | 5/8 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 36
GnomAD4 exome
Cov.:
36
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Monocytopenia with susceptibility to infections Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Department of Immunology, University Hospital Southampton NHSFT | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Pathogenic
D;.;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;P;D
Vest4
MutPred
Loss of glycosylation at P175 (P = 0.0118);Loss of glycosylation at P175 (P = 0.0118);Loss of glycosylation at P175 (P = 0.0118);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at