3-128492886-G-A

Position:

chr3-128492886-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000341105.7(GATA2):c.-46+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00559 in 153,066 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 1 hom., cov: 33)

Exomes 𝑓: 0.016 ( 0 hom. )

Consequence

GATA2
ENST00000341105.7 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.246

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:

GATA2-AS1 (HGNC:51108): (GATA2 antisense RNA 1)

GATA2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 3-128492886-G-A is Benign according to our data. Variant chr3-128492886-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 343144.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-128492886-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00554 (843/152272) while in subpopulation NFE AF= 0.00943 (641/68000). AF 95% confidence interval is 0.00882. There are 1 homozygotes in gnomad4. There are 369 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 843 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA2	NM_032638.5 linkuse as main transcript	c.-46+13C>T		intron_variant		ENST00000341105.7	NP_116027.2
GATA2-AS1	NR_125398.1 linkuse as main transcript	n.759+2817G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA2	ENST00000341105.7 linkuse as main transcript	c.-46+13C>T		intron_variant		1	NM_032638.5	ENSP00000345681	P1	P23769-1
GATA2-AS1	ENST00000669945.1 linkuse as main transcript	n.293+2817G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00554

AC:

843

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00819

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00943

Gnomad OTH

AF:

0.00383

GnomAD4 exome

AF:

0.0164

AC:

AN:

794

Hom.:

Cov.:

AF XY:

0.0146

AC XY:

AN XY:

618

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:

0.167

Gnomad4 NFE exome

AF:

0.0165

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00554

AC:

843

AN:

152272

Hom.:

Cov.:

AF XY:

0.00496

AC XY:

369

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00819

Gnomad4 NFE

AF:

0.00943

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00778

Hom.:

Bravo

AF:

0.00506

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Deafness-lymphedema-leukemia syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.5

DANN

Benign

0.95

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.5

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over