Genetic Variant GATAD2B:c.134-6188G>A (chr1-153796264-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 ENST00000633218.1(ENSG00000291199):n.622C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,752 control chromosomes in the GnomAD database, including 13,988 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 ( 13930 hom., cov: 34)

Exomes 𝑓: 0.46 ( 58 hom. )

Consequence

ENSG00000291199
ENST00000633218.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.340

Publications

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

GATAD2B links:

ENSG00000231827 (HGNC:):

ENSG00000231827 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000633218.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.81).

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: ENST00000633218.1. 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
	LOC343052	NR_126565.1		n.622C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATAD2B	ENST00000637918.1	TSL:5	c.134-6188G>A	intron	N/A	ENSP00000490724.1	A0A1B0GW07
ENSG00000231827	ENST00000427283.1	TSL:6	n.607C>T	non_coding_transcript_exon	Exon 2 of 11
ENSG00000291199	ENST00000633218.1	TSL:3	n.622C>T	non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.410

AC:

62412

AN:

152122

Hom.:

13926

Cov.:

show subpopulations

Gnomad AFR

AF:

0.289

Gnomad AMI

AF:

0.495

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.572

Gnomad EAS

AF:

0.0593

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.430

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.517

Gnomad OTH

AF:

0.433

GnomAD4 exome

AF:

0.455

AC:

233

AN:

512

Hom.:

Cov.:

AF XY:

0.432

AC XY:

140

AN XY:

324

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.452

AC:

199

AN:

440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.563

AC:

AN:

Other (OTH)

AF:

0.417

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

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:

62428

AN:

152240

Hom.:

13930

Cov.:

AF XY:

0.401

AC XY:

29850

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.289

AC:

11994

AN:

41554

American (AMR)

AF:

0.345

AC:

5276

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.572

AC:

1985

AN:

3472

East Asian (EAS)

AF:

0.0590

AC:

306

AN:

5184

South Asian (SAS)

AF:

0.349

AC:

1680

AN:

4818

European-Finnish (FIN)

AF:

0.430

AC:

4561

AN:

10602

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.517

AC:

35126

AN:

67986

Other (OTH)

AF:

0.436

AC:

920

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1891

3782

5674

7565

9456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.367

Hom.:

1464

Bravo

AF:

0.393

Asia WGS

AF:

0.235

AC:

816

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.12

(source)

DANN

Benign

0.77

PhyloP100

-0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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