rs11717152

Positions:

• chr3-128482170-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032638.5(GATA2):​c.1018-226T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 599,928 control chromosomes in the GnomAD database, including 14,978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4195 hom., cov: 33)
  • Exomes 𝑓: 0.21 (10783 hom.)
• Consequence: GATA2 NM_032638.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0550

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-128482170-A-C is Benign according to our data. Variant chr3-128482170-A-C is described in ClinVar as [Benign]. Clinvar id is 1277301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA2	NM_001145661.2	c.1018-226T>G		intron_variant		ENST00000487848.6	NP_001139133.1
GATA2	NM_032638.5	c.1018-226T>G		intron_variant		ENST00000341105.7	NP_116027.2
GATA2	NM_001145662.1	c.1018-268T>G		intron_variant			NP_001139134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7	c.1018-226T>G		intron_variant		1	NM_032638.5	ENSP00000345681	P1
GATA2	ENST00000487848.6	c.1018-226T>G		intron_variant		1	NM_001145661.2	ENSP00000417074	P1
GATA2	ENST00000430265.6	c.1018-268T>G		intron_variant		1		ENSP00000400259
GATA2	ENST00000696466.1	c.1300-226T>G		intron_variant				ENSP00000512647

Frequencies

GnomAD3 genomes AF: 0.230 AC: 35021 AN: 152082 Hom.: 4192 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0997

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.212 AC: 95002 AN: 447728 Hom.: 10783 AF XY: 0.206 AC XY: 48139 AN XY: 234070

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.235

Gnomad4 OTH exome AF: 0.225

GnomAD4 genome AF: 0.230 AC: 35046 AN: 152200 Hom.: 4195 Cov.: 33 AF XY: 0.226 AC XY: 16849 AN XY: 74408

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.230

Alfa AF: 0.235 Hom.: 2112

Bravo AF: 0.236

Asia WGS AF: 0.133 AC: 465 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.77

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

LitVar

Other links and lift over

dbSNP: rs11717152; hg19: chr3-128201013;