rs367785289
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_032638.5(GATA2):c.30G>T(p.Trp10Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,602,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W10L) has been classified as Uncertain significance.
Frequency
Consequence
NM_032638.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA2 | NM_001145661.2 | c.30G>T | p.Trp10Cys | missense_variant | 3/7 | ENST00000487848.6 | |
GATA2 | NM_032638.5 | c.30G>T | p.Trp10Cys | missense_variant | 2/6 | ENST00000341105.7 | |
GATA2 | NM_001145662.1 | c.30G>T | p.Trp10Cys | missense_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA2 | ENST00000341105.7 | c.30G>T | p.Trp10Cys | missense_variant | 2/6 | 1 | NM_032638.5 | P1 | |
GATA2 | ENST00000487848.6 | c.30G>T | p.Trp10Cys | missense_variant | 3/7 | 1 | NM_001145661.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000849 AC: 19AN: 223872Hom.: 0 AF XY: 0.0000902 AC XY: 11AN XY: 121926
GnomAD4 exome AF: 0.000148 AC: 214AN: 1450592Hom.: 0 Cov.: 32 AF XY: 0.000154 AC XY: 111AN XY: 720458
GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74358
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 16, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 26, 2018 | - - |
Monocytopenia with susceptibility to infections Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Johns Hopkins Genomics, Johns Hopkins University | Nov 08, 2019 | This GATA2 variant (rs367785289) is rare (<0.1%) in a large population datasets (gnomAD: 25/255228 total alleles; 0.0098%; no homozygotes). A single submitter in ClinVar classifies the clinical significance of this variant as uncertain5. Three bioinformatic tools queried predict that this substitution would be probably damaging, and the tryptophan residue at this position is evolutionarily conserved across nearly all species assessed. The ClinVar entry for this variant suggests that it may alter exon 2 splicing, however two bioinformatics tools do not support this observation and this variant has not been functionally assessed to our knowledge. Due to lack of functional data, we consider the clinical significance of c.30G>T to be uncertain at this time. - |
Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 28, 2023 | This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 10 of the GATA2 protein (p.Trp10Cys). This variant is present in population databases (rs367785289, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with GATA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 472455). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GATA2 protein function. 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Apr 16, 2021 | - - |
Acute myeloid leukemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 16, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at