dbSNP rs12133923: GATAD2B:c.134-10688G>T (chr1-153800764-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000820544.1(ENSG00000291199):n.296+6559C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 152,362 control chromosomes in the GnomAD database, including 14,563 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 0.42 ( 14498 hom., cov: 31)

Exomes 𝑓: 0.44 ( 65 hom. )

Consequence

ENSG00000291199
ENST00000820544.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.133

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:

ENSG00000231827 (HGNC:):

ENSG00000231827 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=-0.86).

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: ENST00000820544.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATAD2B	ENST00000637918.1	TSL:5	c.134-10688G>T	intron	N/A	ENSP00000490724.1	A0A1B0GW07
ENSG00000231827	ENST00000427283.1	TSL:6	n.1511+52C>A	intron	N/A
ENSG00000291199	ENST00000820544.1		n.296+6559C>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

64129

AN:

151624

Hom.:

14489

Cov.:

show subpopulations

Gnomad AFR

AF:

0.290

Gnomad AMI

AF:

0.493

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.576

Gnomad EAS

AF:

0.149

Gnomad SAS

AF:

0.354

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.516

Gnomad OTH

AF:

0.446

GnomAD4 exome

AF:

0.444

AC:

275

AN:

620

Hom.:

AF XY:

0.424

AC XY:

174

AN XY:

410

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.449

AC:

202

AN:

450

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.424

AC:

AN:

132

Other (OTH)

AF:

0.571

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.423

AC:

64153

AN:

151742

Hom.:

14498

Cov.:

AF XY:

0.416

AC XY:

30849

AN XY:

74166

show subpopulations

African (AFR)

AF:

0.289

AC:

11982

AN:

41400

American (AMR)

AF:

0.432

AC:

6585

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.576

AC:

1998

AN:

3470

East Asian (EAS)

AF:

0.149

AC:

763

AN:

5136

South Asian (SAS)

AF:

0.355

AC:

1705

AN:

4804

European-Finnish (FIN)

AF:

0.434

AC:

4591

AN:

10576

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.516

AC:

35005

AN:

67784

Other (OTH)

AF:

0.449

AC:

948

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1779

3557

5336

7114

8893

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.457

Hom.:

3045

Bravo

AF:

0.414

Asia WGS

AF:

0.279

AC:

971

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.29

(source)

DANN

Benign

0.79

PhyloP100

-0.13

Splicing

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