6-31667889-G-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP2PP3_StrongPP5
The NM_001320.7(CSNK2B):c.94G>A(p.Asp32Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D32A) has been classified as Pathogenic.
Frequency
Consequence
NM_001320.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CSNK2B | NM_001320.7 | c.94G>A | p.Asp32Asn | missense_variant | 3/7 | ENST00000375882.7 | |
CSNK2B | NM_001282385.2 | c.94G>A | p.Asp32Asn | missense_variant | 3/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSNK2B | ENST00000375882.7 | c.94G>A | p.Asp32Asn | missense_variant | 3/7 | 1 | NM_001320.7 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 29
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 15, 2021 | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 520596). This missense change has been observed in individual(s) with CSNK2B-related conditions (PMID: 33644862, 34041744; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with asparagine at codon 32 of the CSNK2B protein (p.Asp32Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 16, 2021 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33644862, 34041744) - |
CSNK2B-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 08, 2023 | The CSNK2B c.94G>A variant is predicted to result in the amino acid substitution p.Asp32Asn. This variant has been reported de novo in an individual with profound developmental delay, intellectual disability, cerebellar atrophy and additional neurologic features (Tables 2 and S1, Subject 329, Hiraide et al. 2021. PubMed ID: 33644862). This variant has also been reported de novo in an additional individual with moderate intellectual disability, wide-based ataxic gait, mild dysmorphic features, and absence seizures (Table S1, Ernst et al. 2021. PubMed ID: 34041744). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Of note, de novo variants in this gene are commonly reported to be causative for CSNK2B-associated disorders (Okur et al. 2016. PubMed ID: 27048600; Nakashima et al. 2019. PubMed ID: 30655572; Li et al. 2019. PubMed ID: 31784560). This variant is interpreted as likely pathogenic. - |
Seizure;C0039075:Syndactyly;C0399526:Mandibular prognathia;C0423224:Deeply set eye;C0424503:Abnormal facial shape;C0426886:Tapered finger;C1168239:Asymmetry of the ears;C1834055:Underdeveloped nasal alae;C1844505:Pointed chin;C1865017:Thin upper lip vermilion;C3714756:Intellectual disability;C4021770:Toe clinodactyly Pathogenic:1
Pathogenic, no assertion criteria provided | research | Cologne Center for Genomics, Faculty of Medicine, University of Cologne | Apr 11, 2022 | Causing a new intellectual disability-craniodigital syndrome (IDCS) - |
Poirier-Bienvenu neurodevelopmental syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Aug 13, 2022 | ACMG classification criteria: PS4 strong, PM2 moderated, PM5 moderated, PM6 moderated, PP2 supporting - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 05, 2016 | - - |
CSNK2B-related intellectual disability with or without epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Oct 01, 2019 | The CSNK2B c.94G>A (p.Asp32Asn) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not found in the Genome Aggregation Database despite good sequence coverage, so the variant is presumed to be rare. Based on the limited evidence, the p.Asp32Asn variant is classified as a variant of unknown significance for CSNK2B-related intellectual disability with or without epilepsy. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at