rs863224874
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_032638.5(GATA2):c.1125_1126insCCTC(p.Tyr376ProfsTer9) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. L375L) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 33)
Consequence
GATA2
NM_032638.5 frameshift
NM_032638.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.672
Genes affected
GATA2 (HGNC:4171): (GATA binding protein 2) This gene encodes a member of the GATA family of zinc-finger transcription factors that are named for the consensus nucleotide sequence they bind in the promoter regions of target genes. The encoded protein plays an essential role in regulating transcription of genes involved in the development and proliferation of hematopoietic and endocrine cell lineages. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 35 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 3-128481836-A-AGAGG is Pathogenic according to our data. Variant chr3-128481836-A-AGAGG is described in ClinVar as [Pathogenic]. Clinvar id is 216932.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA2 | NM_001145661.2 | c.1125_1126insCCTC | p.Tyr376ProfsTer9 | frameshift_variant | 6/7 | ENST00000487848.6 | |
GATA2 | NM_032638.5 | c.1125_1126insCCTC | p.Tyr376ProfsTer9 | frameshift_variant | 5/6 | ENST00000341105.7 | |
GATA2 | NM_001145662.1 | c.1083_1084insCCTC | p.Tyr362ProfsTer9 | frameshift_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA2 | ENST00000341105.7 | c.1125_1126insCCTC | p.Tyr376ProfsTer9 | frameshift_variant | 5/6 | 1 | NM_032638.5 | P1 | |
GATA2 | ENST00000487848.6 | c.1125_1126insCCTC | p.Tyr376ProfsTer9 | frameshift_variant | 6/7 | 1 | NM_001145661.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Deafness-lymphedema-leukemia syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | UCLA Clinical Genomics Center, UCLA | Aug 26, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at