rs45463895

Variant names:

• chr3-128480137-A-T
• rs45463895
• NM_001145661.2:c.*882T>A

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 VariationId 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.

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.*882T>A		3_prime_UTR	Exon 7 of 7	NP_001139133.1	P23769-1
	GATA2	NM_032638.5	MANE Select	c.*882T>A		3_prime_UTR	Exon 6 of 6	NP_116027.2
	GATA2	NM_001145662.1		c.*882T>A		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.*882T>A		3_prime_UTR	Exon 6 of 6	ENSP00000345681.2	P23769-1
	GATA2	ENST00000487848.6	TSL:1 MANE Plus Clinical	c.*882T>A		3_prime_UTR	Exon 7 of 7	ENSP00000417074.1	P23769-1
	GATA2	ENST00000696466.1		c.*882T>A		3_prime_UTR	Exon 8 of 8	ENSP00000512647.1	A0A8Q3WLD0

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

African (AFR) AF: 0.0632 AC: 246 AN: 3892

American (AMR) AF: 0.103 AC: 258 AN: 2498

Ashkenazi Jewish (ASJ) AF: 0.0355 AC: 182 AN: 5124

East Asian (EAS) AF: 0.00746 AC: 85 AN: 11398

South Asian (SAS) AF: 0.0627 AC: 44 AN: 702

European-Finnish (FIN) AF: 0.0500 AC: 3 AN: 60

Middle Eastern (MID) AF: 0.0630 AC: 31 AN: 492

European-Non Finnish (NFE) AF: 0.0513 AC: 2564 AN: 49990

Other (OTH) AF: 0.0525 AC: 355 AN: 6766

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

African (AFR) AF: 0.0626 AC: 2600 AN: 41566

American (AMR) AF: 0.0819 AC: 1253 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0384 AC: 133 AN: 3468

East Asian (EAS) AF: 0.00963 AC: 50 AN: 5190

South Asian (SAS) AF: 0.0779 AC: 376 AN: 4828

European-Finnish (FIN) AF: 0.0283 AC: 301 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0492 AC: 3345 AN: 68042

Other (OTH) AF: 0.0515 AC: 109 AN: 2116

Alfa AF: 0.0482 Hom.: 23

Bravo AF: 0.0568

Asia WGS AF: 0.0450 AC: 156 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Deafness-lymphedema-leukemia syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.4
DANN	Benign	0.82
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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: rs45463895; hg19: chr3-128198980;