chr3-128485741-G-T

Variant names:

• chr3-128485741-G-T
• NM_032638.5:c.857C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032638.5(GATA2):​c.857C>A​(p.Ala286Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,578 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GATA2 NM_032638.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.64

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29344594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA2	NM_032638.5	c.857C>A	p.Ala286Asp	missense_variant	Exon 3 of 6	ENST00000341105.7	NP_116027.2
GATA2	NM_001145661.2	c.857C>A	p.Ala286Asp	missense_variant	Exon 4 of 7		NP_001139133.1
GATA2	NM_001145662.1	c.857C>A	p.Ala286Asp	missense_variant	Exon 3 of 6		NP_001139134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7	c.857C>A	p.Ala286Asp	missense_variant	Exon 3 of 6	1	NM_032638.5	ENSP00000345681.2
GATA2	ENST00000487848.6	c.857C>A	p.Ala286Asp	missense_variant	Exon 4 of 7	1		ENSP00000417074.1
GATA2	ENST00000430265.6	c.857C>A	p.Ala286Asp	missense_variant	Exon 3 of 6	1		ENSP00000400259.2
GATA2	ENST00000696466.1	c.1139C>A	p.Ala380Asp	missense_variant	Exon 5 of 8			ENSP00000512647.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461578 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727066

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.53	D;.;D
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.051
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.73	.;T;T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Uncertain	0.47	D
MutationAssessor	Benign	1.2	L;L;L
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.5	N;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.29	B;B;B
Vest4		0.45
MutPred		0.39		Gain of glycosylation at S290 (P = 0.0135);Gain of glycosylation at S290 (P = 0.0135);Gain of glycosylation at S290 (P = 0.0135);
MVP		0.68
MPC		0.95
ClinPred		0.45	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-128204584;