3-128486227-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_032638.5(GATA2):c.371C>A(p.Thr124Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000032 in 1,561,510 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 (★★).
Frequency
Consequence
NM_032638.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GATA2 | NM_032638.5 | c.371C>A | p.Thr124Lys | missense_variant | Exon 3 of 6 | ENST00000341105.7 | NP_116027.2 | |
GATA2 | NM_001145661.2 | c.371C>A | p.Thr124Lys | missense_variant | Exon 4 of 7 | NP_001139133.1 | ||
GATA2 | NM_001145662.1 | c.371C>A | p.Thr124Lys | missense_variant | Exon 3 of 6 | NP_001139134.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000614 AC: 1AN: 162880Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 86906
GnomAD4 exome AF: 0.00000284 AC: 4AN: 1409252Hom.: 0 Cov.: 36 AF XY: 0.00000287 AC XY: 2AN XY: 695804
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152258Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74434
ClinVar
Submissions by phenotype
not specified Uncertain:1Other:1
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Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections Uncertain:1
This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 124 of the GATA2 protein (p.Thr124Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 134464). 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 with a negative predictive value of 95%. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at