rs777965976
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_032638.5(GATA2):c.50T>A(p.Leu17Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,876 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. L17M) has been classified 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA2 | NM_001145661.2 | c.50T>A | p.Leu17Gln | missense_variant | 3/7 | ENST00000487848.6 | |
GATA2 | NM_032638.5 | c.50T>A | p.Leu17Gln | missense_variant | 2/6 | ENST00000341105.7 | |
GATA2 | NM_001145662.1 | c.50T>A | p.Leu17Gln | missense_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA2 | ENST00000341105.7 | c.50T>A | p.Leu17Gln | missense_variant | 2/6 | 1 | NM_032638.5 | P1 | |
GATA2 | ENST00000487848.6 | c.50T>A | p.Leu17Gln | missense_variant | 3/7 | 1 | NM_001145661.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000422 AC: 1AN: 237106Hom.: 0 AF XY: 0.00000774 AC XY: 1AN XY: 129196
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1456876Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 724204
GnomAD4 genome ? Cov.: 33
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 | Sep 19, 2022 | 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. ClinVar contains an entry for this variant (Variation ID: 539717). This variant has not been reported in the literature in individuals affected with GATA2-related conditions. 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 sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 17 of the GATA2 protein (p.Leu17Gln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at