3-128487036-G-T

Variant names:

• chr3-128487036-G-T
• rs374415484
• NM_032638.5:c.-5C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032638.5(GATA2):​c.-5C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,402,308 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: GATA2 NM_032638.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA2	NM_032638.5	c.-5C>A		5_prime_UTR_variant	Exon 2 of 6	ENST00000341105.7	NP_116027.2
GATA2	NM_001145661.2	c.-5C>A		5_prime_UTR_variant	Exon 3 of 7		NP_001139133.1
GATA2	NM_001145662.1	c.-5C>A		5_prime_UTR_variant	Exon 2 of 6		NP_001139134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7	c.-5C>A		5_prime_UTR_variant	Exon 2 of 6	1	NM_032638.5	ENSP00000345681.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1402308 Hom.: 0 Cov.: 34 AF XY: 0.00000144 AC XY: 1 AN XY: 693500

African (AFR) AF: 0.00 AC: 0 AN: 32234

American (AMR) AF: 0.00 AC: 0 AN: 38174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24910

East Asian (EAS) AF: 0.00 AC: 0 AN: 37280

South Asian (SAS) AF: 0.00 AC: 0 AN: 80482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5422

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078702

Other (OTH) AF: 0.00 AC: 0 AN: 57964

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.0
DANN	Benign	0.97
PhyloP100		-0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=298/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs374415484; hg19: chr3-128205879;