rs781161922
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The ENST00000341105.7(GATA2):c.1331C>T(p.Pro444Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,614,128 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. P444R) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000341105.7 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GATA2 | NM_001145661.2 | c.1331C>T | p.Pro444Leu | missense_variant | 7/7 | ENST00000487848.6 | NP_001139133.1 | |
GATA2 | NM_032638.5 | c.1331C>T | p.Pro444Leu | missense_variant | 6/6 | ENST00000341105.7 | NP_116027.2 | |
GATA2 | NM_001145662.1 | c.1289C>T | p.Pro430Leu | missense_variant | 6/6 | NP_001139134.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GATA2 | ENST00000341105.7 | c.1331C>T | p.Pro444Leu | missense_variant | 6/6 | 1 | NM_032638.5 | ENSP00000345681 | P1 | |
GATA2 | ENST00000487848.6 | c.1331C>T | p.Pro444Leu | missense_variant | 7/7 | 1 | NM_001145661.2 | ENSP00000417074 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152252Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251216Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135798
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461876Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727240
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152252Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74380
ClinVar
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 25, 2023 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 444 of the GATA2 protein (p.Pro444Leu). This variant is present in population databases (rs781161922, gnomAD 0.01%). 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: 574296). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 21, 2024 | Observed in large population cohorts (gnomAD; internal data); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Acute myeloid leukemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 01, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at