rs1806462

Variant names:

• chr3-128487775-C-A
• rs1806462
• NM_001145661.2:c.-110G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-128487775-C-A
• chr3-128487775-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145661.2(GATA2):​c.-110G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,068 control chromosomes in the GnomAD database, including 14,058 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (14039 hom., cov: 32)
  • Exomes 𝑓: 0.39 (19 hom.)
• Consequence: GATA2 NM_001145661.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34
• Publications: 12 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: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• 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: Orphanet, Ambry Genetics
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145661.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA2	NM_001145661.2	MANE Plus Clinical	c.-110G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	NP_001139133.1
	GATA2	NM_001145661.2	MANE Plus Clinical	c.-110G>T		5_prime_UTR	Exon 2 of 7	NP_001139133.1
	GATA2	NM_032638.5	MANE Select	c.-45-699G>T		intron	N/A	NP_116027.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA2	ENST00000487848.6	TSL:1 MANE Plus Clinical	c.-110G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 7	ENSP00000417074.1
	GATA2	ENST00000430265.6	TSL:1	c.-110G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000400259.2
	GATA2	ENST00000487848.6	TSL:1 MANE Plus Clinical	c.-110G>T		5_prime_UTR	Exon 2 of 7	ENSP00000417074.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64443 AN: 151776 Hom.: 14028 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.444

GnomAD4 exome AF: 0.385 AC: 67 AN: 174 Hom.: 19 Cov.: 0 AF XY: 0.355 AC XY: 44 AN XY: 124

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.373 AC: 62 AN: 166

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.425 AC: 64496 AN: 151894 Hom.: 14039 Cov.: 32 AF XY: 0.418 AC XY: 31056 AN XY: 74218

African (AFR) AF: 0.473 AC: 19613 AN: 41430

American (AMR) AF: 0.439 AC: 6702 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1532 AN: 3468

East Asian (EAS) AF: 0.239 AC: 1231 AN: 5142

South Asian (SAS) AF: 0.437 AC: 2106 AN: 4818

European-Finnish (FIN) AF: 0.325 AC: 3431 AN: 10562

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.418 AC: 28353 AN: 67900

Other (OTH) AF: 0.441 AC: 928 AN: 2104

Alfa AF: 0.340 Hom.: 1456

Bravo AF: 0.433

Asia WGS AF: 0.355 AC: 1232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.6
DANN	Benign	0.81
PhyloP100		-2.3
PromoterAI		0.099	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=300/0	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: rs1806462; hg19: chr3-128206618;