rs1169516070
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032638.5(GATA2):c.1372C>T(p.Pro458Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,618 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P458L) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA2 | NM_001145661.2 | c.1372C>T | p.Pro458Ser | missense_variant | 7/7 | ENST00000487848.6 | |
GATA2 | NM_032638.5 | c.1372C>T | p.Pro458Ser | missense_variant | 6/6 | ENST00000341105.7 | |
GATA2 | NM_001145662.1 | c.1330C>T | p.Pro444Ser | missense_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA2 | ENST00000341105.7 | c.1372C>T | p.Pro458Ser | missense_variant | 6/6 | 1 | NM_032638.5 | P1 | |
GATA2 | ENST00000487848.6 | c.1372C>T | p.Pro458Ser | missense_variant | 7/7 | 1 | NM_001145661.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1458618Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 725030
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 | Jun 15, 2017 | In summary, this variant has uncertain impact on GATA2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with a GATA2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 458 of the GATA2 protein (p.Pro458Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at