chr1-153810278-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_020699.4(GATAD2B):c.1681G>A(p.Gly561Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,613,000 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 (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
GATAD2B
NM_020699.4 missense
NM_020699.4 missense
Scores
3
8
7
Clinical Significance
Conservation
PhyloP100: 4.74
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, GATAD2B
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATAD2B | NM_020699.4 | c.1681G>A | p.Gly561Arg | missense_variant | 11/11 | ENST00000368655.5 | |
GATAD2B | XM_047426115.1 | c.1684G>A | p.Gly562Arg | missense_variant | 11/11 | ||
GATAD2B | XM_047426117.1 | c.1681G>A | p.Gly561Arg | missense_variant | 11/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATAD2B | ENST00000368655.5 | c.1681G>A | p.Gly561Arg | missense_variant | 11/11 | 1 | NM_020699.4 | P1 | |
GATAD2B | ENST00000634544.1 | c.1681G>A | p.Gly561Arg | missense_variant | 11/11 | 5 | P1 | ||
GATAD2B | ENST00000634408.1 | c.1633G>A | p.Gly545Arg | missense_variant | 11/11 | 5 | |||
GATAD2B | ENST00000637918.1 | c.135+1453G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152080Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
1
AN:
152080
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 247780Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134180
GnomAD3 exomes
AF:
AC:
4
AN:
247780
Hom.:
AF XY:
AC XY:
1
AN XY:
134180
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460920Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726742
GnomAD4 exome
AF:
AC:
9
AN:
1460920
Hom.:
Cov.:
30
AF XY:
AC XY:
3
AN XY:
726742
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152080Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74268
GnomAD4 genome
?
AF:
AC:
1
AN:
152080
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74268
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
3
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 22, 2023 | 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 variant has not been reported in the literature in individuals affected with GATAD2B-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 561 of the GATAD2B protein (p.Gly561Arg). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.
REVEL
Benign
Sift
Uncertain
D;.;.
Sift4G
Uncertain
D;D;D
Polyphen
D;D;.
Vest4
MutPred
Gain of solvent accessibility (P = 0.019);Gain of solvent accessibility (P = 0.019);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 32
Find out detailed SpliceAI scores and Pangolin per-transcript scores at