rs114542403

Positions:

chr1-153813440-G-C

Variant summary

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

The ENST00000368655.5(GATAD2B):c.1229C>G(p.Ala410Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000292 in 1,613,526 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

GATAD2B
ENST00000368655.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.28

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=0.006309688).

BP6

Variant 1-153813440-G-C is Benign according to our data. Variant chr1-153813440-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 211065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 247 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GATAD2B	NM_020699.4 linkuse as main transcript	c.1229C>G	p.Ala410Gly	missense_variant	8/11	ENST00000368655.5	NP_065750.1
GATAD2B	XM_047426115.1 linkuse as main transcript	c.1232C>G	p.Ala411Gly	missense_variant	8/11		XP_047282071.1
GATAD2B	XM_047426117.1 linkuse as main transcript	c.1229C>G	p.Ala410Gly	missense_variant	8/11		XP_047282073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GATAD2B	ENST00000368655.5 linkuse as main transcript	c.1229C>G	p.Ala410Gly	missense_variant	8/11	1	NM_020699.4	ENSP00000357644	P1
GATAD2B	ENST00000634544.1 linkuse as main transcript	c.1229C>G	p.Ala410Gly	missense_variant	8/11	5		ENSP00000489184	P1
GATAD2B	ENST00000634408.1 linkuse as main transcript	c.1181C>G	p.Ala394Gly	missense_variant	8/11	5		ENSP00000489595
GATAD2B	ENST00000634564.1 linkuse as main transcript	c.485C>G	p.Ala162Gly	missense_variant	3/5	5		ENSP00000489309

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

247

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00582

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000370

AC:

AN:

251108

Hom.:

AF XY:

0.000273

AC XY:

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.00523

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000153

AC:

224

AN:

1461298

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.00571

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.00162

AC:

247

AN:

152228

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.00580

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000272

Hom.:

Bravo

AF:

0.00185

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000379

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2020	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 23, 2016

- -

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

0.072

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

T;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

0.062

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.80

.;.;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.0063

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.075

N;N;.

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.7

N;.;.

REVEL

Benign

0.12

Sift

Benign

0.16

T;.;.

Sift4G

Benign

0.41

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.18

MVP

0.12

MPC

0.81

ClinPred

0.034

GERP RS

5.2

Varity_R

0.17

gMVP

0.26

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