Genetic Variant GATAD2B:c.*3417G>A (chr1-153806760-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.*3417G>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 0.141 in 130,780 control chromosomes in the GnomAD database, including 1,615 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 0.14 ( 1607 hom., cov: 26)

Exomes 𝑓: 0.20 ( 8 hom. )

Consequence

GATAD2B
NM_020699.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0690

Publications

7 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 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.*3417G>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.*3417G>A	3_prime_UTR	Exon 11 of 11	ENSP00000357644.4	Q8WXI9
GATAD2B	ENST00000637918.1	TSL:5	c.133+4971G>A	intron	N/A	ENSP00000490724.1	A0A1B0GW07
ENSG00000291199	ENST00000820544.1		n.296+12555C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

18296

AN:

130238

Hom.:

1609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0745

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.0994

Gnomad EAS

AF:

0.505

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.126

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.141

GnomAD4 exome

AF:

0.199

AC:

AN:

438

Hom.:

Cov.:

AF XY:

0.214

AC XY:

AN XY:

262

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.199

AC:

AN:

428

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.140

AC:

18291

AN:

130342

Hom.:

1607

Cov.:

AF XY:

0.150

AC XY:

9342

AN XY:

62452

show subpopulations

African (AFR)

AF:

0.0745

AC:

2514

AN:

33764

American (AMR)

AF:

0.117

AC:

1386

AN:

11856

Ashkenazi Jewish (ASJ)

AF:

0.0994

AC:

310

AN:

3118

East Asian (EAS)

AF:

0.505

AC:

2483

AN:

4918

South Asian (SAS)

AF:

0.173

AC:

707

AN:

4092

European-Finnish (FIN)

AF:

0.246

AC:

2044

AN:

8298

Middle Eastern (MID)

AF:

0.128

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.136

AC:

8363

AN:

61428

Other (OTH)

AF:

0.142

AC:

252

AN:

1770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

730

1460

2191

2921

3651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

202

404

606

808

1010

<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:

0.0811

Hom.:

157

Bravo

AF:

0.115

Asia WGS

AF:

0.268

AC:

929

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.3

(source)

DANN

Benign

0.66

PhyloP100

-0.069

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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