rs1553188463
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_020699.4(GATAD2B):c.535C>T(p.Arg179Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GATAD2B
NM_020699.4 stop_gained
NM_020699.4 stop_gained
Scores
3
3
1
Clinical Significance
Conservation
PhyloP100: 0.988
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 16 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
?
Variant 1-153818853-G-A is Pathogenic according to our data. Variant chr1-153818853-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 435290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-153818853-G-A is described in Lovd as [Pathogenic]. Variant chr1-153818853-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATAD2B | NM_020699.4 | c.535C>T | p.Arg179Ter | stop_gained | 4/11 | ENST00000368655.5 | |
GATAD2B | XM_047426115.1 | c.538C>T | p.Arg180Ter | stop_gained | 4/11 | ||
GATAD2B | XM_047426117.1 | c.535C>T | p.Arg179Ter | stop_gained | 4/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATAD2B | ENST00000368655.5 | c.535C>T | p.Arg179Ter | stop_gained | 4/11 | 1 | NM_020699.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1461086Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726936
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1461086
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
726936
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome Pathogenic:3
Pathogenic, no assertion criteria provided | research | Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 01, 2015 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 29, 2023 | This sequence change creates a premature translational stop signal (p.Arg179*) in the GATAD2B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GATAD2B are known to be pathogenic (PMID: 23033978, 25356899, 27159321). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 435290). This premature translational stop signal has been observed in individual(s) with GATAD2B-associated neurodevelopmental disorder (PMID: 32688057). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Mar 23, 2018 | The R179X variant in the GATAD2B gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R179X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R179X as a pathogenic variant, - |
Intellectual disability Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Diagnostic Laboratory, Strasbourg University Hospital | Sep 10, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at