rs753645971
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_032638.5(GATA2):c.445G>A(p.Gly149Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000582 in 1,581,142 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G149A) has been classified as Uncertain significance.
Frequency
Consequence
NM_032638.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA2 | NM_001145661.2 | c.445G>A | p.Gly149Arg | missense_variant | 4/7 | ENST00000487848.6 | |
GATA2 | NM_032638.5 | c.445G>A | p.Gly149Arg | missense_variant | 3/6 | ENST00000341105.7 | |
GATA2 | NM_001145662.1 | c.445G>A | p.Gly149Arg | missense_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA2 | ENST00000341105.7 | c.445G>A | p.Gly149Arg | missense_variant | 3/6 | 1 | NM_032638.5 | P1 | |
GATA2 | ENST00000487848.6 | c.445G>A | p.Gly149Arg | missense_variant | 4/7 | 1 | NM_001145661.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000122 AC: 23AN: 188602Hom.: 0 AF XY: 0.0000884 AC XY: 9AN XY: 101812
GnomAD4 exome AF: 0.0000553 AC: 79AN: 1428958Hom.: 0 Cov.: 36 AF XY: 0.0000509 AC XY: 36AN XY: 707590
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74348
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 28, 2020 | DNA sequence analysis of the GATA2 gene demonstrated a sequence change, c.445G>A, in exon 3 that results in an amino acid change, p.Gly149Arg. This sequence change does not appear to have been previously described in patients with GATA2-related disorders and has been described in the gnomAD database with a frequency of 0.053% in the Latino sub-population (dbSNP rs753645971). The p.Gly149Arg change affects a poorly conserved amino acid residue located in a domain of the GATA2 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Gly149Arg substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Gly149Arg change remains unknown at this time. - |
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 | Oct 31, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 11, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in a patient with gastric cancer and in a patient with leukemia (AML); however, it is unclear whether the variant was germline or somatic in the latter individual (Aguirre-Ruiz et al., 2020; Herrera-Pariente et al., 2021); This variant is associated with the following publications: (PMID: 30755392, 33255857, 33525650) - |
Acute myeloid leukemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Feb 12, 2024 | - - |
GATA2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 17, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at