Genetic Variant GATAD2B:p.Ser586Ser (chr1-153810201-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_020699.4(GATAD2B):c.1758G>A(p.Ser586Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000041 in 1,611,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

GATAD2B
NM_020699.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00800

Publications

0 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 1-153810201-C-T is Benign according to our data. Variant chr1-153810201-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1933860.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.008 with no splicing effect.

BS2

High AC in GnomAdExome4 at 62 AD gene.

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.1758G>A	p.Ser586Ser	synonymous	Exon 11 of 11	NP_065750.1	Q8WXI9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GATAD2B	ENST00000368655.5	TSL:1 MANE Select	c.1758G>A	p.Ser586Ser	synonymous	Exon 11 of 11	ENSP00000357644.4	Q8WXI9
GATAD2B	ENST00000634544.1	TSL:5	c.1758G>A	p.Ser586Ser	synonymous	Exon 11 of 11	ENSP00000489184.1	Q8WXI9
GATAD2B	ENST00000867096.1		c.1758G>A	p.Ser586Ser	synonymous	Exon 12 of 12	ENSP00000537155.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000201

AC:

AN:

248798

AF XY:

0.00000742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000425

AC:

AN:

1459426

Hom.:

Cov.:

AF XY:

0.0000482

AC XY:

AN XY:

725976

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33328

American (AMR)

AF:

0.00

AC:

AN:

44218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39554

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85848

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000513

AC:

AN:

1110946

Other (OTH)

AF:

0.0000332

AC:

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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:

0.0000263

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41422

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.64

PhyloP100

-0.0080

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

polymorphism

(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