3-128486824-C-A
Variant summary
Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_032638.5(GATA2):c.208G>T(p.Val70Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000218 in 1,608,808 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). Synonymous variant affecting the same amino acid position (i.e. V70V) has been classified as Likely benign.
Frequency
Consequence
NM_032638.5 missense
Scores
Clinical Significance
Conservation
Publications
- deafness-lymphedema-leukemia syndromeInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
- GATA2 deficiency with susceptibility to MDS/AMLInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- monocytopenia with susceptibility to infectionsInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
- acute myeloid leukemiaInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- myelodysplastic syndromeInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
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ACMG classification
Our verdict: Benign. The variant received -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GATA2 | NM_032638.5 | c.208G>T | p.Val70Phe | missense_variant | Exon 2 of 6 | ENST00000341105.7 | NP_116027.2 | |
GATA2 | NM_001145661.2 | c.208G>T | p.Val70Phe | missense_variant | Exon 3 of 7 | NP_001139133.1 | ||
GATA2 | NM_001145662.1 | c.208G>T | p.Val70Phe | missense_variant | Exon 2 of 6 | NP_001139134.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152280Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000892 AC: 21AN: 235372 AF XY: 0.0000705 show subpopulations
GnomAD4 exome AF: 0.0000220 AC: 32AN: 1456410Hom.: 0 Cov.: 32 AF XY: 0.0000207 AC XY: 15AN XY: 724002 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152398Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74522 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
GATA2 deficiency with susceptibility to MDS/AML Uncertain:1
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Acute myeloid leukemia;C3279664:Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections;C3463824:Myelodysplastic syndrome Uncertain:1
This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.1% (20/17588) (https://gnomad.broadinstitute.org/variant/3-128205667-C-A?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:472452). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -
not provided Uncertain:1
In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31723772) -
Acute myeloid leukemia Uncertain:1
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Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at