3-128480322-G-A

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.*697C>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 0.00111 in 233,422 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00081 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (0 hom.)
• Consequence: GATA2 NM_032638.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.671

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=-0.68).
• BP6: Variant 3-128480322-G-A is Benign according to our data. Variant chr3-128480322-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 343118.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000807 (123/152346) while in subpopulation SAS AF= 0.00187 (9/4824). AF 95% confidence interval is 0.000973. There are 1 homozygotes in gnomad4. There are 64 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 123 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA2	NM_001145661.2	c.*697C>T		3_prime_UTR_variant	7/7	ENST00000487848.6
GATA2	NM_032638.5	c.*697C>T		3_prime_UTR_variant	6/6	ENST00000341105.7
GATA2	NM_001145662.1	c.*697C>T		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA2	ENST00000341105.7	c.*697C>T		3_prime_UTR_variant	6/6	1	NM_032638.5	P1
GATA2	ENST00000487848.6	c.*697C>T		3_prime_UTR_variant	7/7	1	NM_001145661.2	P1

Frequencies

GnomAD3 genomes AF: 0.000808 AC: 123 AN: 152228 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000719

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00101

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00169 AC: 137 AN: 81076 Hom.: 0 Cov.: 0 AF XY: 0.00199 AC XY: 74 AN XY: 37276

Gnomad4 AFR exome AF: 0.000257

Gnomad4 AMR exome AF: 0.000400

Gnomad4 ASJ exome AF: 0.00761

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00162

Gnomad4 OTH exome AF: 0.00162

GnomAD4 genome AF: 0.000807 AC: 123 AN: 152346 Hom.: 1 Cov.: 33 AF XY: 0.000859 AC XY: 64 AN XY: 74486

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000718

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00101

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000278 Hom.: 0

Bravo AF: 0.000812

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Deafness-lymphedema-leukemia syndrome Benign:1

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	0.95
Dann	Benign	0.84

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: rs45437196; hg19: chr3-128199165;