3-128480137-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032638.5(GATA2):c.*882T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0513 in 233,262 control chromosomes in the GnomAD database, including 382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.054 (281 hom., cov: 33)
  • Exomes 𝑓: 0.047 (101 hom.)
• Consequence: GATA2 NM_032638.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.237

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 3-128480137-A-T is Benign according to our data. Variant chr3-128480137-A-T is described in ClinVar as [Benign]. Clinvar id is 343116.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA2	NM_001145661.2	c.*882T>A		3_prime_UTR_variant	7/7	ENST00000487848.6
GATA2	NM_032638.5	c.*882T>A		3_prime_UTR_variant	6/6	ENST00000341105.7
GATA2	NM_001145662.1	c.*882T>A		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA2	ENST00000341105.7	c.*882T>A		3_prime_UTR_variant	6/6	1	NM_032638.5	P1
GATA2	ENST00000487848.6	c.*882T>A		3_prime_UTR_variant	7/7	1	NM_001145661.2	P1

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8191 AN: 152222 Hom.: 279 Cov.: 33

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0815

Gnomad ASJ AF: 0.0384

Gnomad EAS AF: 0.00961

Gnomad SAS AF: 0.0786

Gnomad FIN AF: 0.0283

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0491

Gnomad OTH AF: 0.0511

GnomAD4 exome AF: 0.0466 AC: 3768 AN: 80922 Hom.: 101 Cov.: 0 AF XY: 0.0452 AC XY: 1680 AN XY: 37190

Gnomad4 AFR exome AF: 0.0632

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.0355

Gnomad4 EAS exome AF: 0.00746

Gnomad4 SAS exome AF: 0.0627

Gnomad4 FIN exome AF: 0.0500

Gnomad4 NFE exome AF: 0.0513

Gnomad4 OTH exome AF: 0.0525

GnomAD4 genome AF: 0.0538 AC: 8202 AN: 152340 Hom.: 281 Cov.: 33 AF XY: 0.0534 AC XY: 3978 AN XY: 74488

Gnomad4 AFR AF: 0.0626

Gnomad4 AMR AF: 0.0819

Gnomad4 ASJ AF: 0.0384

Gnomad4 EAS AF: 0.00963

Gnomad4 SAS AF: 0.0779

Gnomad4 FIN AF: 0.0283

Gnomad4 NFE AF: 0.0492

Gnomad4 OTH AF: 0.0515

Alfa AF: 0.0482 Hom.: 23

Bravo AF: 0.0568

Asia WGS AF: 0.0450 AC: 156 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Deafness-lymphedema-leukemia syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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	-0.56
Cadd	Benign	6.4
Dann	Benign	0.82

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: rs45463895; hg19: chr3-128198980;