GeneBe

NM_032638.5:c.801C>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_032638.5(GATA2):​c.801C>G​(p.Pro267Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P267P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GATA2
NM_032638.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -10.3

Publications

0 publications found
Variant links:
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]
GATA2 Gene-Disease associations (from GenCC):
  • deafness-lymphedema-leukemia syndrome
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
  • GATA2 deficiency with susceptibility to MDS/AML
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • monocytopenia with susceptibility to infections
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
  • acute myeloid leukemia
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
  • myelodysplastic syndrome
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP7
Synonymous conserved (PhyloP=-10.3 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GATA2NM_032638.5 linkc.801C>G p.Pro267Pro synonymous_variant Exon 3 of 6 ENST00000341105.7 NP_116027.2 P23769-1
GATA2NM_001145661.2 linkc.801C>G p.Pro267Pro synonymous_variant Exon 4 of 7 NP_001139133.1 P23769-1
GATA2NM_001145662.1 linkc.801C>G p.Pro267Pro synonymous_variant Exon 3 of 6 NP_001139134.1 P23769-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GATA2ENST00000341105.7 linkc.801C>G p.Pro267Pro synonymous_variant Exon 3 of 6 1 NM_032638.5 ENSP00000345681.2 P23769-1
GATA2ENST00000487848.6 linkc.801C>G p.Pro267Pro synonymous_variant Exon 4 of 7 1 ENSP00000417074.1 P23769-1
GATA2ENST00000430265.6 linkc.801C>G p.Pro267Pro synonymous_variant Exon 3 of 6 1 ENSP00000400259.2 P23769-2
GATA2ENST00000696466.1 linkc.1083C>G p.Pro361Pro synonymous_variant Exon 5 of 8 ENSP00000512647.1 A0A8Q3WLD0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461704
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727136
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44708
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26124
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53352
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111936
Other (OTH)
AF:
0.00
AC:
0
AN:
60386
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.010
DANN
Benign
0.79
PhyloP100
-10
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs376351188; hg19: chr3-128204640; API