chr1-153812083-G-A

Position:

chr1-153812083-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2

The ENST00000368655.5(GATAD2B):c.1469C>T(p.Ala490Val) variant causes a missense change. The variant allele was found at a frequency of 0.00616 in 1,613,156 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 38 hom. )

Consequence

GATAD2B
ENST00000368655.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.97

Variant links:

Genes affected

GATAD2B (HGNC:30778): (GATA zinc finger domain containing 2B) This gene encodes a zinc finger protein transcriptional repressor. The encoded protein is part of the methyl-CpG-binding protein-1 complex, which represses gene expression by deacetylating methylated nucleosomes. Mutations in this gene are linked to intellectual disability and dysmorphic features associated with cognitive disability. [provided by RefSeq, Jun 2016]

GATAD2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), GATAD2B. . Gene score misZ 3.161 (greater than the threshold 3.09). Trascript score misZ 3.9812 (greater than threshold 3.09). GenCC has associacion of gene with severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066090226).

BP6

Variant 1-153812083-G-A is Benign according to our data. Variant chr1-153812083-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 211066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 658 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GATAD2B	NM_020699.4 linkuse as main transcript	c.1469C>T	p.Ala490Val	missense_variant	9/11	ENST00000368655.5	NP_065750.1
GATAD2B	XM_047426115.1 linkuse as main transcript	c.1472C>T	p.Ala491Val	missense_variant	9/11		XP_047282071.1
GATAD2B	XM_047426117.1 linkuse as main transcript	c.1469C>T	p.Ala490Val	missense_variant	9/11		XP_047282073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATAD2B	ENST00000368655.5 linkuse as main transcript	c.1469C>T	p.Ala490Val	missense_variant	9/11	1	NM_020699.4	ENSP00000357644	P1

Frequencies

GnomAD3 genomes

AF:

0.00432

AC:

658

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00754

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00464

AC:

1166

AN:

251342

Hom.:

AF XY:

0.00461

AC XY:

626

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.000595

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00431

Gnomad NFE exome

AF:

0.00816

Gnomad OTH exome

AF:

0.00505

GnomAD4 exome

AF:

0.00635

AC:

9275

AN:

1460872

Hom.:

Cov.:

AF XY:

0.00603

AC XY:

4386

AN XY:

726784

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00237

Gnomad4 ASJ exome

AF:

0.000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00498

Gnomad4 NFE exome

AF:

0.00766

Gnomad4 OTH exome

AF:

0.00489

GnomAD4 genome

AF:

0.00432

AC:

658

AN:

152284

Hom.:

Cov.:

AF XY:

0.00398

AC XY:

296

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.00754

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00659

Hom.:

Bravo

AF:

0.00439

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00733

AC:

ExAC

AF:

0.00521

AC:

632

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00731

EpiControl

AF:

0.00776

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	GATAD2B: BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 26, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 05, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 08, 2014

- -

Severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

T;T;.

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.83

.;.;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.0066

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L;.

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.74

N;.;.

REVEL

Benign

0.077

Sift

Benign

0.13

T;.;.

Sift4G

Benign

0.27

T;T;T

Polyphen

0.60

P;P;.

Vest4

0.20

MVP

0.14

MPC

0.80

ClinPred

0.0062

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.69

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