3-128486117-G-T

Position:

• chr3-128486117-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032638.5(GATA2):​c.481C>A​(p.Pro161Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,459,444 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P161A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GATA2 NM_032638.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.21

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA2	NM_032638.5	c.481C>A	p.Pro161Thr	missense_variant	3/6	ENST00000341105.7	NP_116027.2
GATA2	NM_001145661.2	c.481C>A	p.Pro161Thr	missense_variant	4/7		NP_001139133.1
GATA2	NM_001145662.1	c.481C>A	p.Pro161Thr	missense_variant	3/6		NP_001139134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7	c.481C>A	p.Pro161Thr	missense_variant	3/6	1	NM_032638.5	ENSP00000345681.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000124 AC: 3 AN: 241956 Hom.: 0 AF XY: 0.0000152 AC XY: 2 AN XY: 131336

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000146

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1459444 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 725784

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: 0.0000378

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;.;T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.065
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.73	.;T;T
M_CAP	Pathogenic	0.33	D
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Uncertain	0.50	D
MutationAssessor	Benign	1.8	L;L;L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.25	N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.24	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.48	P;D;P
Vest4		0.67
MutPred		0.23		Loss of glycosylation at P161 (P = 0.0461);Loss of glycosylation at P161 (P = 0.0461);Loss of glycosylation at P161 (P = 0.0461);
MVP		0.76
MPC		1.6
ClinPred		0.36	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs34799090; hg19: chr3-128204960;