rs3803

chr3-128480537-G-A

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.*482C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 251,374 control chromosomes in the GnomAD database, including 3,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2468 hom., cov: 33)
  • Exomes 𝑓: 0.16 (1475 hom.)
• Consequence: GATA2 NM_032638.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.819

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=-0.81).
• BP6: Variant 3-128480537-G-A is Benign according to our data. Variant chr3-128480537-G-A is described in ClinVar as [Benign]. Clinvar id is 343123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA2	NM_001145661.2	c.*482C>T		3_prime_UTR_variant	7/7	ENST00000487848.6
GATA2	NM_032638.5	c.*482C>T		3_prime_UTR_variant	6/6	ENST00000341105.7
GATA2	NM_001145662.1	c.*482C>T		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA2	ENST00000341105.7	c.*482C>T		3_prime_UTR_variant	6/6	1	NM_032638.5	P1
GATA2	ENST00000487848.6	c.*482C>T		3_prime_UTR_variant	7/7	1	NM_001145661.2	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26494 AN: 152006 Hom.: 2467 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0549

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.181

GnomAD4 exome AF: 0.164 AC: 16278 AN: 99250 Hom.: 1475 Cov.: 0 AF XY: 0.165 AC XY: 7685 AN XY: 46594

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.0514

Gnomad4 SAS exome AF: 0.0904

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.174 AC: 26509 AN: 152124 Hom.: 2468 Cov.: 33 AF XY: 0.171 AC XY: 12738 AN XY: 74378

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0549

Gnomad4 SAS AF: 0.0737

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.179

Alfa AF: 0.189 Hom.: 4931

Bravo AF: 0.174

Asia WGS AF: 0.0720 AC: 250 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Deafness-lymphedema-leukemia syndrome;C3280030:Monocytopenia with susceptibility to infections Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 11, 2022

- -

Deafness-lymphedema-leukemia syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	8.1
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3803; hg19: chr3-128199380;