chr20-486439-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_177559.3(CSNK2A1):c.997C>T(p.Arg333Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000124 in 1,613,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
CSNK2A1
NM_177559.3 stop_gained
NM_177559.3 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 4.22
Genes affected
CSNK2A1 (HGNC:2457): (casein kinase 2 alpha 1) Casein kinase II is a serine/threonine protein kinase that phosphorylates acidic proteins such as casein. It is involved in various cellular processes, including cell cycle control, apoptosis, and circadian rhythm. The kinase exists as a tetramer and is composed of an alpha, an alpha-prime, and two beta subunits. The alpha subunits contain the catalytic activity while the beta subunits undergo autophosphorylation. The protein encoded by this gene represents the alpha subunit. Multiple transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Apr 2018]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.152 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 20-486439-G-A is Pathogenic according to our data. Variant chr20-486439-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 989368.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CSNK2A1 | NM_177559.3 | c.997C>T | p.Arg333Ter | stop_gained | 13/14 | ENST00000217244.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSNK2A1 | ENST00000217244.9 | c.997C>T | p.Arg333Ter | stop_gained | 13/14 | 1 | NM_177559.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000660 AC: 1AN: 151448Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461620Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 727152
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GnomAD4 genome ? AF: 0.00000660 AC: 1AN: 151448Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 73886
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
CSNK2A1-related neurodevelopmental syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 04, 2019 | The CSNK2A1 c.997C>T (p.Arg333Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. 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 and is in a region of good sequencing coverage so the variant is presumed to be rare. The p.Arg333Ter variant is located barely outside of the protein kinase domain, where the majority of reported pathogenic missense variants are located. Based on the de novo state of the variant and its rarity, the CSNK2A1 p.Arg333Ter variant is classified as likely pathogenic for CSNK2A1-related neurodevelopmental syndrome. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A;A
Vest4
0.93, 0.93
GERP RS
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