dbSNP rs775573177: GATA2:p.Gln38His (chr3-128486918-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_032638.5(GATA2):c.114G>T(p.Gln38His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,538 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GATA2
NM_032638.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
GATA2	NM_032638.5 link	c.114G>T	p.Gln38His	missense_variant	Exon 2 of 6	ENST00000341105.7	NP_116027.2	P23769-1
GATA2	NM_001145661.2 link	c.114G>T	p.Gln38His	missense_variant	Exon 3 of 7		NP_001139133.1	P23769-1
GATA2	NM_001145662.1 link	c.114G>T	p.Gln38His	missense_variant	Exon 2 of 6		NP_001139134.1	P23769-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7 link	c.114G>T	p.Gln38His	missense_variant	Exon 2 of 6	1	NM_032638.5	ENSP00000345681.2		P23769-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460538

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726518

show subpopulations

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:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Dec 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.Q38H variant (also known as c.114G>T), located in coding exon 1 of the GATA2 gene, results from a G to T substitution at nucleotide position 114. The glutamine at codon 38 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

D;.;D;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.82

.;T;T;T

M_CAP

Pathogenic

0.52

MetaRNN

Uncertain

0.57

D;D;D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Uncertain

2.4

M;M;M;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.6

N;N;N;D

REVEL

Pathogenic

0.67

Sift

Benign

0.071

T;T;T;D

Sift4G

Benign

0.55

T;T;T;D

Polyphen

0.97

D;D;D;.

Vest4

0.44

MutPred

0.40

Gain of glycosylation at Y33 (P = 0.001);Gain of glycosylation at Y33 (P = 0.001);Gain of glycosylation at Y33 (P = 0.001);Gain of glycosylation at Y33 (P = 0.001);

MVP

0.80

MPC

1.4

ClinPred

0.95

GERP RS

4.6

Varity_R

0.28

gMVP

0.57

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over