rs145131801

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_020699.4(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
NM_020699.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.97

Publications

13 publications found

Variant links:

COSMIC-nc: COSV64083539

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 Gene-Disease associations (from GenCC):

severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Illumina

GATAD2B links:

ENSG00000291199 (HGNC:):

ENSG00000291199 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

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 Benign/Likely_benign. ClinVar VariationId is 211066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 658 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020699.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATAD2B	NM_020699.4	MANE Select	c.1469C>T	p.Ala490Val	missense	Exon 9 of 11	NP_065750.1	Q8WXI9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GATAD2B	ENST00000368655.5	TSL:1 MANE Select	c.1469C>T	p.Ala490Val	missense	Exon 9 of 11	ENSP00000357644.4	Q8WXI9
GATAD2B	ENST00000634544.1	TSL:5	c.1469C>T	p.Ala490Val	missense	Exon 9 of 11	ENSP00000489184.1	Q8WXI9
GATAD2B	ENST00000867096.1		c.1469C>T	p.Ala490Val	missense	Exon 10 of 12	ENSP00000537155.1

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

GnomAD2 exomes

AF:

0.00464

AC:

1166

AN:

251342

AF XY:

0.00461

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 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

African (AFR)

AF:

0.000986

AC:

AN:

33458

American (AMR)

AF:

0.00237

AC:

106

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000765

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00498

AC:

266

AN:

53380

Middle Eastern (MID)

AF:

0.00536

AC:

AN:

5592

European-Non Finnish (NFE)

AF:

0.00766

AC:

8518

AN:

1111294

Other (OTH)

AF:

0.00489

AC:

295

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

413

826

1238

1651

2064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

324

648

972

1296

1620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00432

AC:

658

AN:

152284

Hom.:

Cov.:

AF XY:

0.00398

AC XY:

296

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00116

AC:

AN:

41542

American (AMR)

AF:

0.00333

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00264

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00754

AC:

513

AN:

68032

Other (OTH)

AF:

0.00521

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

132

165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00631

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

not specified (1)

Severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.83

M_CAP

Benign

0.0070

MetaRNN

Benign

0.0066

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

5.0

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.74

REVEL

Benign

0.077

Sift

Benign

0.13

Sift4G

Benign

0.27

Polyphen

0.60

Vest4

0.20

MVP

0.14

MPC

0.80

ClinPred

0.0062

GERP RS

5.7

PromoterAI

-0.043

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.69

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over