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: ClinGen, G2P, Illumina, Orphanet, Labcorp Genetics (formerly Invitae)

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GATAD2B	NM_020699.4 link	c.*3417G>A	3_prime_UTR_variant	Exon 11 of 11	ENST00000368655.5	NP_065750.1	Q8WXI9
GATAD2B	XM_047426115.1 link	c.*3417G>A	3_prime_UTR_variant	Exon 11 of 11		XP_047282071.1
GATAD2B	XM_047426117.1 link	c.*3417G>A	3_prime_UTR_variant	Exon 11 of 11		XP_047282073.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GATAD2B	ENST00000368655.5 link	c.*3417G>A	3_prime_UTR_variant	Exon 11 of 11	1	NM_020699.4	ENSP00000357644.4	Q8WXI9
GATAD2B	ENST00000637918.1 link	c.133+4971G>A	intron_variant	Intron 2 of 3	5		ENSP00000490724.1	A0A1B0GW07
ENSG00000291199	ENST00000820544.1 link	n.296+12555C>T	intron_variant	Intron 1 of 1

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 v4.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over