rs374457534
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_032638.5(GATA2):c.1232C>T(p.Ala411Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000471 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A411A) has been classified as Benign.
Frequency
Consequence
NM_032638.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GATA2 | NM_001145661.2 | c.1232C>T | p.Ala411Val | missense_variant | 7/7 | ENST00000487848.6 | NP_001139133.1 | |
GATA2 | NM_032638.5 | c.1232C>T | p.Ala411Val | missense_variant | 6/6 | ENST00000341105.7 | NP_116027.2 | |
GATA2 | NM_001145662.1 | c.1190C>T | p.Ala397Val | missense_variant | 6/6 | NP_001139134.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GATA2 | ENST00000341105.7 | c.1232C>T | p.Ala411Val | missense_variant | 6/6 | 1 | NM_032638.5 | ENSP00000345681 | P1 | |
GATA2 | ENST00000487848.6 | c.1232C>T | p.Ala411Val | missense_variant | 7/7 | 1 | NM_001145661.2 | ENSP00000417074 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251460Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135920
GnomAD4 exome AF: 0.0000506 AC: 74AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.0000550 AC XY: 40AN XY: 727246
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74358
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 19, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 411 of the GATA2 protein (p.Ala411Val). This variant is present in population databases (rs374457534, 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: 472438). 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. - |
Acute myeloid leukemia;C3279664:Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections;C3463824:Myelodysplastic syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 16, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 24, 2023 | 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 - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Aug 26, 2021 | - - |
Acute myeloid leukemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 13, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at