rs1230061825

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_020699.4(GATAD2B):c.1459C>T(p.Pro487Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,612,848 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P487P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

GATAD2B
NM_020699.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 7.62

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: 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.33973318).

BS2

High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD2B	NM_020699.4 link	c.1459C>T	p.Pro487Ser	missense_variant	Exon 9 of 11	ENST00000368655.5	NP_065750.1	Q8WXI9
GATAD2B	XM_047426115.1 link	c.1462C>T	p.Pro488Ser	missense_variant	Exon 9 of 11		XP_047282071.1
GATAD2B	XM_047426117.1 link	c.1459C>T	p.Pro487Ser	missense_variant	Exon 9 of 11		XP_047282073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD2B	ENST00000368655.5 link	c.1459C>T	p.Pro487Ser	missense_variant	Exon 9 of 11	1	NM_020699.4	ENSP00000357644.4		Q8WXI9

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152180

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1460668

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726684

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.0000180

AC:

AN:

1111054

Other (OTH)

AF:

0.00

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 18, 2015

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Uncertain:1

May 20, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with GATAD2B-related conditions. ClinVar contains an entry for this variant (Variation ID: 435287). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GATAD2B protein function. This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 487 of the GATAD2B protein (p.Pro487Ser). This variant is not present in population databases (gnomAD no frequency). -

Severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome

Uncertain:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

T;T;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.85

.;.;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L;.

PhyloP100

7.6

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-2.3

N;.;.

REVEL

Benign

0.13

Sift

Benign

0.10

T;.;.

Sift4G

Benign

0.48

T;T;T

Polyphen

0.98

D;D;.

Vest4

0.49

MutPred

0.19

Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);.;

MVP

0.12

MPC

1.9

ClinPred

0.87

GERP RS

5.7

PromoterAI

-0.043

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.67

Mutation Taster

=52/48

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over