3-128486005-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_032638.5(GATA2):c.593C>T(p.Ala198Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,614,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. A198S) has been classified as Uncertain significance.
Frequency
Consequence
NM_032638.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA2 | NM_001145661.2 | c.593C>T | p.Ala198Val | missense_variant | 4/7 | ENST00000487848.6 | |
GATA2 | NM_032638.5 | c.593C>T | p.Ala198Val | missense_variant | 3/6 | ENST00000341105.7 | |
GATA2 | NM_001145662.1 | c.593C>T | p.Ala198Val | missense_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA2 | ENST00000341105.7 | c.593C>T | p.Ala198Val | missense_variant | 3/6 | 1 | NM_032638.5 | P1 | |
GATA2 | ENST00000487848.6 | c.593C>T | p.Ala198Val | missense_variant | 4/7 | 1 | NM_001145661.2 | P1 | |
GATA2 | ENST00000430265.6 | c.593C>T | p.Ala198Val | missense_variant | 3/6 | 1 | |||
GATA2 | ENST00000696466.1 | c.875C>T | p.Ala292Val | missense_variant | 5/8 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250950Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135818
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461880Hom.: 0 Cov.: 33 AF XY: 0.0000124 AC XY: 9AN XY: 727238
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74342
ClinVar
Submissions by phenotype
Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 198 of the GATA2 protein (p.Ala198Val). This variant is present in population databases (rs745726293, gnomAD 0.008%). 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: 539714). 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 | Aug 18, 2021 | - - |
Acute myeloid leukemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 04, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at