chr3-128480819-G-A

Position:

• chr3-128480819-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.*200C>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 0.228 in 582,460 control chromosomes in the GnomAD database, including 16,277 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4035 hom., cov: 33)
  • Exomes 𝑓: 0.23 (12242 hom.)
• Consequence: GATA2 NM_032638.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.342

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=-0.83).
• BP6: Variant 3-128480819-G-A is Benign according to our data. Variant chr3-128480819-G-A is described in ClinVar as [Benign]. Clinvar id is 343127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA2	NM_001145661.2	c.*200C>T		3_prime_UTR_variant	7/7	ENST00000487848.6	NP_001139133.1
GATA2	NM_032638.5	c.*200C>T		3_prime_UTR_variant	6/6	ENST00000341105.7	NP_116027.2
GATA2	NM_001145662.1	c.*200C>T		3_prime_UTR_variant	6/6		NP_001139134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7	c.*200C>T		3_prime_UTR_variant	6/6	1	NM_032638.5	ENSP00000345681	P1
GATA2	ENST00000487848.6	c.*200C>T		3_prime_UTR_variant	7/7	1	NM_001145661.2	ENSP00000417074	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34115 AN: 152064 Hom.: 4031 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.230 AC: 98915 AN: 430278 Hom.: 12242 Cov.: 5 AF XY: 0.225 AC XY: 49843 AN XY: 221842

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.221

Gnomad4 EAS exome AF: 0.131

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.256

Gnomad4 OTH exome AF: 0.241

GnomAD4 genome AF: 0.224 AC: 34132 AN: 152182 Hom.: 4035 Cov.: 33 AF XY: 0.221 AC XY: 16435 AN XY: 74390

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.239

Alfa AF: 0.247 Hom.: 1487

Bravo AF: 0.228

Asia WGS AF: 0.133 AC: 466 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

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	-0.83
CADD	Benign	0.53
DANN	Benign	0.59
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: rs10934857; hg19: chr3-128199662;