20-483959-C-T

Variant names:

• chr20-483959-C-T
• rs142948288
• NM_177559.3:c.*2G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_177559.3(CSNK2A1):​c.*2G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000647 in 1,610,634 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00064 (1 hom.)
• Consequence: CSNK2A1 NM_177559.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.727
• Publications: 0 publications found

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]

CSNK2A1 Gene-Disease associations (from GenCC):

• Okur-Chung neurodevelopmental syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Illumina, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 20-483959-C-T is Benign according to our data. Variant chr20-483959-C-T is described in ClinVar as Benign. ClinVar VariationId is 1249520.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000696 (106/152210) while in subpopulation NFE AF = 0.000632 (43/68030). AF 95% confidence interval is 0.000482. There are 0 homozygotes in GnomAd4. There are 45 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 106 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177559.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK2A1	NM_177559.3	MANE Select	c.*2G>A		3_prime_UTR	Exon 14 of 14	NP_808227.1	P68400-1
	CSNK2A1	NM_001362770.2		c.*2G>A		3_prime_UTR	Exon 14 of 15	NP_001349699.1	P68400-1
	CSNK2A1	NM_001362771.2		c.*2G>A		3_prime_UTR	Exon 13 of 14	NP_001349700.1	P68400-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK2A1	ENST00000217244.9	TSL:1 MANE Select	c.*2G>A		3_prime_UTR	Exon 14 of 14	ENSP00000217244.3	P68400-1
	CSNK2A1	ENST00000349736.10	TSL:1	c.*2G>A		3_prime_UTR	Exon 12 of 12	ENSP00000339247.6	P68400-2
	CSNK2A1	ENST00000400227.8	TSL:1	c.1060+2417G>A		intron	N/A	ENSP00000383086.3	E7EU96

Frequencies

GnomAD3 genomes AF: 0.000696 AC: 106 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000964 AC: 239 AN: 247888 AF XY: 0.000924

Gnomad AFR exome AF: 0.000191

Gnomad AMR exome AF: 0.000438

Gnomad ASJ exome AF: 0.0141

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0000928

Gnomad NFE exome AF: 0.000581

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.000642 AC: 936 AN: 1458424 Hom.: 1 Cov.: 30 AF XY: 0.000644 AC XY: 467 AN XY: 725500

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000301 AC: 1 AN: 33200

American (AMR) AF: 0.000451 AC: 20 AN: 44334

Ashkenazi Jewish (ASJ) AF: 0.0155 AC: 403 AN: 25956

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39426

South Asian (SAS) AF: 0.0000699 AC: 6 AN: 85786

European-Finnish (FIN) AF: 0.000262 AC: 14 AN: 53370

Middle Eastern (MID) AF: 0.000909 AC: 5 AN: 5502

European-Non Finnish (NFE) AF: 0.000376 AC: 418 AN: 1110638

Other (OTH) AF: 0.00113 AC: 68 AN: 60212

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000696 AC: 106 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.000605 AC XY: 45 AN XY: 74358

African (AFR) AF: 0.000145 AC: 6 AN: 41456

American (AMR) AF: 0.000131 AC: 2 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4836

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68030

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.00232 Hom.: 0

Bravo AF: 0.000771

EpiCase AF: 0.000873

EpiControl AF: 0.000535

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	CSNK2A1-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs142948288; hg19: chr20-464603; COSMIC: COSV99424535;