Genetic Variant GATAD2B:c.729+15G>A (chr1-153818025-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020699.4(GATAD2B):c.729+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,579,648 control chromosomes in the GnomAD database, including 75,549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6099 hom., cov: 32)

Exomes 𝑓: 0.31 ( 69450 hom. )

Consequence

GATAD2B
NM_020699.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.803

Publications

13 publications found

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 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-153818025-C-T is Benign according to our data. Variant chr1-153818025-C-T is described in ClinVar as Benign. ClinVar VariationId is 1285293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

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.729+15G>A		intron	N/A	NP_065750.1	Q8WXI9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATAD2B	ENST00000368655.5	TSL:1 MANE Select	c.729+15G>A	intron	N/A	ENSP00000357644.4	Q8WXI9
GATAD2B	ENST00000634544.1	TSL:5	c.729+15G>A	intron	N/A	ENSP00000489184.1	Q8WXI9
GATAD2B	ENST00000867096.1		c.729+15G>A	intron	N/A	ENSP00000537155.1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40777

AN:

152012

Hom.:

6100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.285

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.309

Gnomad OTH

AF:

0.295

GnomAD2 exomes

AF:

0.322

AC:

73044

AN:

226758

AF XY:

0.325

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.439

Gnomad ASJ exome

AF:

0.317

Gnomad EAS exome

AF:

0.273

Gnomad FIN exome

AF:

0.340

Gnomad NFE exome

AF:

0.321

Gnomad OTH exome

AF:

0.337

GnomAD4 exome

AF:

0.309

AC:

440395

AN:

1427518

Hom.:

69450

Cov.:

AF XY:

0.310

AC XY:

219783

AN XY:

708702

show subpopulations

African (AFR)

AF:

0.117

AC:

3734

AN:

31790

American (AMR)

AF:

0.431

AC:

16325

AN:

37840

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

7534

AN:

24452

East Asian (EAS)

AF:

0.302

AC:

11728

AN:

38810

South Asian (SAS)

AF:

0.334

AC:

27258

AN:

81610

European-Finnish (FIN)

AF:

0.344

AC:

18202

AN:

52870

Middle Eastern (MID)

AF:

0.353

AC:

1966

AN:

5570

European-Non Finnish (NFE)

AF:

0.307

AC:

335964

AN:

1095702

Other (OTH)

AF:

0.300

AC:

17684

AN:

58874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

13243

26486

39729

52972

66215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11008

22016

33024

44032

55040

<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:

0.268

AC:

40790

AN:

152130

Hom.:

6099

Cov.:

AF XY:

0.273

AC XY:

20311

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.126

AC:

5233

AN:

41524

American (AMR)

AF:

0.386

AC:

5897

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

1049

AN:

3470

East Asian (EAS)

AF:

0.286

AC:

1478

AN:

5174

South Asian (SAS)

AF:

0.333

AC:

1609

AN:

4826

European-Finnish (FIN)

AF:

0.343

AC:

3615

AN:

10554

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.309

AC:

20995

AN:

67982

Other (OTH)

AF:

0.292

AC:

616

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1476

2952

4427

5903

7379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.293

Hom.:

2981

Bravo

AF:

0.268

Asia WGS

AF:

0.285

AC:

994

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.7

(source)

DANN

Benign

0.79

PhyloP100

-0.80

PromoterAI

0.010

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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