3-128481942-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_032638.5(GATA2):​c.1020G>A​(p.Ser340Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

GATA2
NM_032638.5 splice_region, synonymous

Scores

2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:3

Conservation

PhyloP100: -1.55
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 Likely_benign. Variant got -5 ACMG points.

BP6
Variant 3-128481942-C-T is Benign according to our data. Variant chr3-128481942-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 539721.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=3, Likely_benign=2}.
BS2
High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GATA2NM_032638.5 linkc.1020G>A p.Ser340Ser splice_region_variant, synonymous_variant 5/6 ENST00000341105.7 NP_116027.2 P23769-1
GATA2NM_001145661.2 linkc.1020G>A p.Ser340Ser splice_region_variant, synonymous_variant 6/7 NP_001139133.1 P23769-1
GATA2NM_001145662.1 linkc.1018-40G>A intron_variant NP_001139134.1 P23769-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GATA2ENST00000341105.7 linkc.1020G>A p.Ser340Ser splice_region_variant, synonymous_variant 5/61 NM_032638.5 ENSP00000345681.2 P23769-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152152
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000387
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000562
AC:
14
AN:
249282
Hom.:
0
AF XY:
0.0000518
AC XY:
7
AN XY:
135166
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000203
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000218
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000178
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461104
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
726844
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152270
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000388
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000303
Hom.:
0
Bravo
AF:
0.00000756
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:3
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 20, 2024The c.1020G>A variant (also known as p.S340S), located in coding exon 4 of the GATA2 gene, results from a G to A substitution at nucleotide position 1020. This nucleotide substitution does not change the at codon 340. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice acceptor site. Based on the available evidence, the clinical significance of this variant remains unclear. -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxNov 18, 2022In silico analysis supports a deleterious effect on splicing; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26287967) -
Acute myeloid leukemia Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingBaylor GeneticsJun 23, 2023- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoSep 28, 2020- -
GATA2-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJul 27, 2022This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
CADD
Benign
18
DANN
Benign
0.91
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
4.2

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.93
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.93
Position offset: -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: rs370166358; hg19: chr3-128200785; API