NM_032638.5:c.*546C>T

Variant names:

• chr3-128480473-G-A
• rs45463801
• NM_001145661.2:c.*546C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032638.5(GATA2):​c.*546C>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 0.0349 in 238,984 control chromosomes in the GnomAD database, including 182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (83 hom., cov: 33)
  • Exomes 𝑓: 0.043 (99 hom.)
• Consequence: GATA2 NM_032638.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.20
• Publications: 2 publications found

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]

GATA2 Gene-Disease associations (from GenCC):

• deafness-lymphedema-leukemia syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• GATA2 deficiency with susceptibility to MDS/AML

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• monocytopenia with susceptibility to infections

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
• acute myeloid leukemia

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• myelodysplastic syndrome

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-128480473-G-A is Benign according to our data. Variant chr3-128480473-G-A is described in ClinVar as Benign. ClinVar VariationId is 343120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0738 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032638.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA2	NM_001145661.2	MANE Plus Clinical	c.*546C>T		3_prime_UTR	Exon 7 of 7	NP_001139133.1	P23769-1
	GATA2	NM_032638.5	MANE Select	c.*546C>T		3_prime_UTR	Exon 6 of 6	NP_116027.2
	GATA2	NM_001145662.1		c.*546C>T		3_prime_UTR	Exon 6 of 6	NP_001139134.1	P23769-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA2	ENST00000341105.7	TSL:1 MANE Select	c.*546C>T		3_prime_UTR	Exon 6 of 6	ENSP00000345681.2	P23769-1
	GATA2	ENST00000487848.6	TSL:1 MANE Plus Clinical	c.*546C>T		3_prime_UTR	Exon 7 of 7	ENSP00000417074.1	P23769-1
	GATA2	ENST00000430265.6	TSL:1	c.*546C>T		3_prime_UTR	Exon 6 of 6	ENSP00000400259.2	P23769-2

Frequencies

GnomAD3 genomes AF: 0.0306 AC: 4660 AN: 152210 Hom.: 82 Cov.: 33

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0541

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.0803

Gnomad SAS AF: 0.0253

Gnomad FIN AF: 0.00762

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.0311

GnomAD4 exome AF: 0.0425 AC: 3685 AN: 86656 Hom.: 99 Cov.: 0 AF XY: 0.0421 AC XY: 1688 AN XY: 40138

African (AFR) AF: 0.0141 AC: 57 AN: 4038

American (AMR) AF: 0.0705 AC: 188 AN: 2666

Ashkenazi Jewish (ASJ) AF: 0.0370 AC: 195 AN: 5266

East Asian (EAS) AF: 0.0806 AC: 951 AN: 11804

South Asian (SAS) AF: 0.0208 AC: 16 AN: 770

European-Finnish (FIN) AF: 0.0117 AC: 7 AN: 600

Middle Eastern (MID) AF: 0.0426 AC: 22 AN: 516

European-Non Finnish (NFE) AF: 0.0368 AC: 1986 AN: 53908

Other (OTH) AF: 0.0371 AC: 263 AN: 7088

GnomAD4 genome AF: 0.0306 AC: 4663 AN: 152328 Hom.: 83 Cov.: 33 AF XY: 0.0304 AC XY: 2266 AN XY: 74486

African (AFR) AF: 0.0130 AC: 540 AN: 41586

American (AMR) AF: 0.0540 AC: 827 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3470

East Asian (EAS) AF: 0.0801 AC: 415 AN: 5178

South Asian (SAS) AF: 0.0255 AC: 123 AN: 4824

European-Finnish (FIN) AF: 0.00762 AC: 81 AN: 10630

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0359 AC: 2439 AN: 68016

Other (OTH) AF: 0.0308 AC: 65 AN: 2112

Alfa AF: 0.0330 Hom.: 15

Bravo AF: 0.0346

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Deafness-lymphedema-leukemia syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.095
DANN	Benign	0.58
PhyloP100		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs45463801; hg19: chr3-128199316;