chr3-128485769-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032638.5(GATA2):​c.829A>C​(p.Ser277Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S277G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

GATA2
NM_032638.5 missense

Scores

4
6
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.06
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36128256).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GATA2NM_001145661.2 linkuse as main transcriptc.829A>C p.Ser277Arg missense_variant 4/7 ENST00000487848.6 NP_001139133.1
GATA2NM_032638.5 linkuse as main transcriptc.829A>C p.Ser277Arg missense_variant 3/6 ENST00000341105.7 NP_116027.2
GATA2NM_001145662.1 linkuse as main transcriptc.829A>C p.Ser277Arg missense_variant 3/6 NP_001139134.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GATA2ENST00000341105.7 linkuse as main transcriptc.829A>C p.Ser277Arg missense_variant 3/61 NM_032638.5 ENSP00000345681 P1P23769-1
GATA2ENST00000487848.6 linkuse as main transcriptc.829A>C p.Ser277Arg missense_variant 4/71 NM_001145661.2 ENSP00000417074 P1P23769-1
GATA2ENST00000430265.6 linkuse as main transcriptc.829A>C p.Ser277Arg missense_variant 3/61 ENSP00000400259 P23769-2
GATA2ENST00000696466.1 linkuse as main transcriptc.1111A>C p.Ser371Arg missense_variant 5/8 ENSP00000512647

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.89
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.66
D;.;D
Eigen
Benign
-0.037
Eigen_PC
Benign
0.093
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.79
.;T;T
M_CAP
Pathogenic
0.40
D
MetaRNN
Benign
0.36
T;T;T
MetaSVM
Uncertain
0.70
D
MutationAssessor
Benign
1.6
L;L;L
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-2.0
N;N;N
REVEL
Uncertain
0.42
Sift
Benign
0.040
D;T;D
Sift4G
Benign
0.11
T;T;T
Polyphen
0.040
B;B;B
Vest4
0.40
MutPred
0.32
Gain of MoRF binding (P = 0.0106);Gain of MoRF binding (P = 0.0106);Gain of MoRF binding (P = 0.0106);
MVP
0.72
MPC
1.5
ClinPred
0.83
D
GERP RS
4.6
Varity_R
0.35
gMVP
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs141800945; hg19: chr3-128204612; API