chr3-128486057-C-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032638.5(GATA2):c.541G>C(p.Val181Leu) variant causes a missense 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
GATA2
NM_032638.5 missense
NM_032638.5 missense
Scores
6
9
4
Clinical Significance
Conservation
PhyloP100: 7.42
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GATA2 | NM_001145661.2 | c.541G>C | p.Val181Leu | missense_variant | 4/7 | ENST00000487848.6 | NP_001139133.1 | |
GATA2 | NM_032638.5 | c.541G>C | p.Val181Leu | missense_variant | 3/6 | ENST00000341105.7 | NP_116027.2 | |
GATA2 | NM_001145662.1 | c.541G>C | p.Val181Leu | missense_variant | 3/6 | NP_001139134.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GATA2 | ENST00000341105.7 | c.541G>C | p.Val181Leu | missense_variant | 3/6 | 1 | NM_032638.5 | ENSP00000345681 | P1 | |
GATA2 | ENST00000487848.6 | c.541G>C | p.Val181Leu | missense_variant | 4/7 | 1 | NM_001145661.2 | ENSP00000417074 | P1 | |
GATA2 | ENST00000430265.6 | c.541G>C | p.Val181Leu | missense_variant | 3/6 | 1 | ENSP00000400259 | |||
GATA2 | ENST00000696466.1 | c.823G>C | p.Val275Leu | missense_variant | 5/8 | ENSP00000512647 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
35
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 23, 2020 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GATA2 protein function. This variant has not been reported in the literature in individuals with GATA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with leucine at codon 181 of the GATA2 protein (p.Val181Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N
REVEL
Pathogenic
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
P;B;P
Vest4
MutPred
Loss of glycosylation at P178 (P = 0.0127);Loss of glycosylation at P178 (P = 0.0127);Loss of glycosylation at P178 (P = 0.0127);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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
Publications
No publications associated with this variant yet.