Genetic Variant GATAD2B:c.*2355G>A (chr1-153807822-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020699.4(GATAD2B):c.*2355G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,356 control chromosomes in the GnomAD database, including 13,939 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.41 ( 13888 hom., cov: 30)

Exomes 𝑓: 0.45 ( 51 hom. )

Consequence

GATAD2B
NM_020699.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.898

Publications

12 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.512 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.*2355G>A		3_prime_UTR	Exon 11 of 11	NP_065750.1	Q8WXI9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATAD2B	ENST00000368655.5	TSL:1 MANE Select	c.*2355G>A	3_prime_UTR	Exon 11 of 11	ENSP00000357644.4	Q8WXI9
GATAD2B	ENST00000637918.1	TSL:5	c.133+3909G>A	intron	N/A	ENSP00000490724.1	A0A1B0GW07
ENSG00000291199	ENST00000820544.1		n.296+13617C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.410

AC:

62239

AN:

151760

Hom.:

13884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.289

Gnomad AMI

AF:

0.496

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.572

Gnomad EAS

AF:

0.0585

Gnomad SAS

AF:

0.347

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.517

Gnomad OTH

AF:

0.432

GnomAD4 exome

AF:

0.452

AC:

215

AN:

476

Hom.:

Cov.:

AF XY:

0.429

AC XY:

126

AN XY:

294

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.447

AC:

195

AN:

436

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.600

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.410

AC:

62256

AN:

151880

Hom.:

13888

Cov.:

AF XY:

0.401

AC XY:

29743

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.288

AC:

11932

AN:

41404

American (AMR)

AF:

0.344

AC:

5256

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.572

AC:

1983

AN:

3464

East Asian (EAS)

AF:

0.0584

AC:

303

AN:

5186

South Asian (SAS)

AF:

0.347

AC:

1672

AN:

4812

European-Finnish (FIN)

AF:

0.429

AC:

4521

AN:

10528

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.517

AC:

35101

AN:

67930

Other (OTH)

AF:

0.435

AC:

912

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1740

3480

5219

6959

8699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

590

1180

1770

2360

2950

<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:

0.467

Hom.:

18108

Bravo

AF:

0.394

Asia WGS

AF:

0.235

AC:

818

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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