8-42318599-T-TG
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001556.3(IKBKB):c.1292dup(p.Gln432ProfsTer62) variant causes a frameshift change involving the alteration of a 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
IKBKB
NM_001556.3 frameshift
NM_001556.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.97
Genes affected
IKBKB (HGNC:5960): (inhibitor of nuclear factor kappa B kinase subunit beta) The protein encoded by this gene phosphorylates the inhibitor in the inhibitor/NF-kappa-B complex, causing dissociation of the inhibitor and activation of NF-kappa-B. The encoded protein itself is found in a complex of proteins. Several transcript variants, some protein-coding and some not, have been found for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 8-42318599-T-TG is Pathogenic according to our data. Variant chr8-42318599-T-TG is described in ClinVar as [Pathogenic]. Clinvar id is 102445.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IKBKB | NM_001556.3 | c.1292dup | p.Gln432ProfsTer62 | frameshift_variant | 13/22 | ENST00000520810.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IKBKB | ENST00000520810.6 | c.1292dup | p.Gln432ProfsTer62 | frameshift_variant | 13/22 | 1 | NM_001556.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
IKBKB-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 20, 2024 | The IKBKB c.1292dupG variant is predicted to result in a frameshift and premature protein termination (p.Gln432Profs*62). This variant has been reported in the homozygous state in several individuals with IKBKB-related immune deficiency (Pannicke et al. 2013. PubMed ID: 24369075; Rubin et al. 2018. PubMed ID: 30288645; Cuvelier et al. 2019. PubMed ID: 30391351). This variant has not been reported in a large population database, indicating this variant is rare. Frameshift variants in IKBKB are expected to be pathogenic. This variant is interpreted as pathogenic. - |
Severe combined immunodeficiency due to IKK2 deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 26, 2013 | - - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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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