ClinVar Genomic variation as it relates to human health
NM_177559.3(CSNK2A1):c.468T>A (p.Asp156Glu)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_177559.3(CSNK2A1):c.468T>A (p.Asp156Glu)
Variation ID: 421395 Accession: VCV000421395.8
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 20p13 20: 495761 (GRCh38) [ NCBI UCSC ] 20: 476405 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 27, 2017 Dec 17, 2023 Jan 31, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_177559.3:c.468T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_808227.1:p.Asp156Glu missense NM_001362770.2:c.468T>A NP_001349699.1:p.Asp156Glu missense NM_001362771.2:c.468T>A NP_001349700.1:p.Asp156Glu missense NM_001895.4:c.468T>A NP_001886.1:p.Asp156Glu missense NM_177560.3:c.60T>A NP_808228.1:p.Asp20Glu missense NC_000020.11:g.495761A>T NC_000020.10:g.476405A>T NG_011970.2:g.53078T>A - Protein change
- D156E, D20E
- Other names
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- Canonical SPDI
- NC_000020.11:495760:A:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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CSNK2A1 | Some evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
179 | 255 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
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The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Likely pathogenic (1) |
criteria provided, single submitter
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Jun 4, 2016 | RCV000479609.1 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Jan 31, 2023 | RCV001249615.7 |
Submissions - Germline
Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
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Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Jun 04, 2016)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000570585.4
First in ClinVar: Apr 27, 2017 Last updated: Apr 27, 2017 |
Comment:
The D156E variant in the CSNK2A1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The … (more)
The D156E variant in the CSNK2A1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D156E variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D156E variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. The D156E variant is a strong candidate for a pathogenic variant. (less)
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Pathogenic
(Aug 08, 2018)
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criteria provided, single submitter
Method: clinical testing
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Okur-Chung neurodevelopmental syndrome
Affected status: yes
Allele origin:
germline
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Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital
Accession: SCV001423645.1
First in ClinVar: Jul 25, 2020 Last updated: Jul 25, 2020 |
Comment:
[ACMG/AMP: PS2, PM1, PM2, PM5, PP2, PP3, PP5] This alteration is de novo in origin as it was not detected in the submitted parental specimens … (more)
[ACMG/AMP: PS2, PM1, PM2, PM5, PP2, PP3, PP5] This alteration is de novo in origin as it was not detected in the submitted parental specimens (identity confirmed) [PS2], is located in a mutational hotspot and/or critical and well-established functional domain [PM1], is absent from or rarely observed in large-scale population databases [PM2], is a novel missense change at an amino residue where a different missense change has been deemed to be pathogenic [PM5], is a missense variant in a gene in which missense variants are a common mechanism of disease [PP2], is predicted to be damaging by multiple functional prediction tools [PP3], was reported as a pathogenic/likely pathogenic alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory) [PP5]. (less)
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Pathogenic
(Jan 31, 2023)
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criteria provided, single submitter
Method: clinical testing
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Okur-Chung neurodevelopmental syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004175430.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
Comment:
The CSNK2A1 c.468T>A variant is classified as Pathogenic (PS2, PS4_Supporting, PM5_Supporting, PM2, PP2, PP3) The CSNK2A1 c.468T>A variant is a single nucleotide change in exon … (more)
The CSNK2A1 c.468T>A variant is classified as Pathogenic (PS2, PS4_Supporting, PM5_Supporting, PM2, PP2, PP3) The CSNK2A1 c.468T>A variant is a single nucleotide change in exon 7/13 of the CSNK2A1 gene, which is predicted to change the amino acid aspartic acid at position 156 in the protein to glutamic acid. This variant has been identified as a de novo variant in this patient (PS2). The variant has been reported once in the literature with a clinical presentation of Okur-Chung neurodevelopmental syndrome (Miller et al, 2020; PMID:32371413 (PS4_Supporting). This variant is absent from population databases (PM2). This is a missense variant in a constrained gene where missense variants are a common mechanism of disease and benign variation is rare (GnomAD Z-score= 3.71) (PP2). This variant is a missense change at an amino acid residue where a different missense change p.Asp156His has been seen before (Trinh et al, 2017; PMID: 28725024) (PM5_supporting). Computational predictions support a deleterious effect on the gene or gene product (PP3). The variant has been reported in dbSNP (rs1064795110) and in the HGMD database: CM2016384. It has been reported as Pathogenic/Likely pathogenic by other diagnostic laboratories (ClinVar Variation ID: 421395). (less)
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Likely pathogenic
(Jul 02, 2018)
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no assertion criteria provided
Method: provider interpretation
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Okur-Chung neurodevelopmental syndrome
Affected status: yes
Allele origin:
de novo
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GenomeConnect - Simons Searchlight
Accession: SCV001443594.1
First in ClinVar: Nov 19, 2020 Last updated: Nov 19, 2020 |
Comment:
Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-07-02 and interpreted as Likely Pathogenic. Variant was … (more)
Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-07-02 and interpreted as Likely Pathogenic. Variant was initially reported on 2016-06-13 by GTR ID of laboratory name 26957. The reporting laboratory might also submit to ClinVar. (less)
Sex: male
Testing laboratory: GeneDx
Date variant was reported to submitter: 2016-06-13
Testing laboratory interpretation: Likely pathogenic
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Disease-associated mosaic variation in clinical exome sequencing: a two-year pediatric tertiary care experience. | Miller CR | Cold Spring Harbor molecular case studies | 2020 | PMID: 32371413 |
A novel de novo mutation in CSNK2A1: reinforcing the link to neurodevelopmental abnormalities and dysmorphic features. | Trinh J | Journal of human genetics | 2017 | PMID: 28725024 |
Text-mined citations for rs1064795110 ...
HelpRecord last updated Dec 17, 2023
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.