rs1064793829
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_020699.4(GATAD2B):c.918del(p.Pro307HisfsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
GATAD2B
NM_020699.4 frameshift
NM_020699.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.214
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 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-153816570-GA-G is Pathogenic according to our data. Variant chr1-153816570-GA-G is described in ClinVar as [Pathogenic]. Clinvar id is 419376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATAD2B | NM_020699.4 | c.918del | p.Pro307HisfsTer12 | frameshift_variant | 7/11 | ENST00000368655.5 | |
GATAD2B | XM_047426115.1 | c.921del | p.Pro308HisfsTer12 | frameshift_variant | 7/11 | ||
GATAD2B | XM_047426117.1 | c.918del | p.Pro307HisfsTer12 | frameshift_variant | 7/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATAD2B | ENST00000368655.5 | c.918del | p.Pro307HisfsTer12 | frameshift_variant | 7/11 | 1 | NM_020699.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing;provider interpretation | Geisinger Autism and Developmental Medicine Institute, Geisinger Health System | Feb 26, 2017 | This 7 year old male with mild-moderate intellectual disability, childhood apraxia of speech, macrocephaly (>98th percentile), mild neuromotor abnormalities, and anisocoria was found to carry a de novo 1 bp deletion in the GATAD2B gene. Pathogenic variants in this gene are associated with intellectual disability, limited language development, esotropia, and dysmorphic features. This patient has been noted to have macrocephaly with mild scaphocephaly, a broad forehead, an extra hair whorl, palpebral fissures with slight downward slant, and slightly anteverted nares. This variant is absent from population databases, and it is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. - |
Pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Aug 15, 2019 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31949314) - |
Computational scores
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Calibrated prediction
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at