3-128480304-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_032638.5(GATA2):c.*715G>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 0.021 in 233,388 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (62 hom., cov: 33)
  • Exomes 𝑓: 0.025 (45 hom.)
• Consequence: GATA2 NM_032638.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.102

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=-0.52).
• BP6: Variant 3-128480304-C-T is Benign according to our data. Variant chr3-128480304-C-T is described in ClinVar as [Benign]. Clinvar id is 343117.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-128480304-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0189 (2883/152342) while in subpopulation NFE AF= 0.0261 (1776/68030). AF 95% confidence interval is 0.0251. There are 62 homozygotes in gnomad4. There are 1382 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 2884 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA2	NM_001145661.2	c.*715G>A		3_prime_UTR_variant	7/7	ENST00000487848.6
GATA2	NM_032638.5	c.*715G>A		3_prime_UTR_variant	6/6	ENST00000341105.7
GATA2	NM_001145662.1	c.*715G>A		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA2	ENST00000341105.7	c.*715G>A		3_prime_UTR_variant	6/6	1	NM_032638.5	P1
GATA2	ENST00000487848.6	c.*715G>A		3_prime_UTR_variant	7/7	1	NM_001145661.2	P1

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2884 AN: 152224 Hom.: 62 Cov.: 33

Gnomad AFR AF: 0.00494

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0261

Gnomad OTH AF: 0.0296

GnomAD4 exome AF: 0.0249 AC: 2021 AN: 81046 Hom.: 45 Cov.: 0 AF XY: 0.0261 AC XY: 973 AN XY: 37264

Gnomad4 AFR exome AF: 0.00385

Gnomad4 AMR exome AF: 0.0252

Gnomad4 ASJ exome AF: 0.0625

Gnomad4 EAS exome AF: 0.0000876

Gnomad4 SAS exome AF: 0.00855

Gnomad4 FIN exome AF: 0.0161

Gnomad4 NFE exome AF: 0.0281

Gnomad4 OTH exome AF: 0.0263

GnomAD4 genome AF: 0.0189 AC: 2883 AN: 152342 Hom.: 62 Cov.: 33 AF XY: 0.0186 AC XY: 1382 AN XY: 74490

Gnomad4 AFR AF: 0.00493

Gnomad4 AMR AF: 0.0217

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00622

Gnomad4 FIN AF: 0.0190

Gnomad4 NFE AF: 0.0261

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.0261 Hom.: 23

Bravo AF: 0.0195

Asia WGS AF: 0.00577 AC: 21 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	-0.52
Cadd	Benign	6.6
Dann	Benign	0.84
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: rs73203415; hg19: chr3-128199147;