chr20-483804-A-AT

Variant names:

• chr20-483804-A-AT
• rs111818075
• NM_177559.3:c.*156dupA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_177559.3(CSNK2A1):​c.*156dupA variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00493 in 416,610 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00025 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0075 (0 hom.)
• Consequence: CSNK2A1 NM_177559.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.86
• Publications: 1 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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000254 (38/149364) while in subpopulation SAS AF = 0.00064 (3/4690). AF 95% confidence interval is 0.000271. There are 1 homozygotes in GnomAd4. There are 16 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 38 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.*156dupA		3_prime_UTR	Exon 14 of 14	NP_808227.1	P68400-1
	CSNK2A1	NM_001895.4		c.*156dupA		3_prime_UTR	Exon 13 of 13	NP_001886.1	P68400-1
	CSNK2A1	NM_177560.3		c.*156dupA		3_prime_UTR	Exon 12 of 12	NP_808228.1	P68400-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK2A1	ENST00000217244.9	TSL:1 MANE Select	c.*156dupA		3_prime_UTR	Exon 14 of 14	ENSP00000217244.3	P68400-1
	CSNK2A1	ENST00000349736.10	TSL:1	c.*156dupA		3_prime_UTR	Exon 12 of 12	ENSP00000339247.6	P68400-2
	CSNK2A1	ENST00000400227.8	TSL:1	c.1060+2571dupA		intron	N/A	ENSP00000383086.3	E7EU96

Frequencies

GnomAD3 genomes AF: 0.000255 AC: 38 AN: 149256 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.000639

Gnomad FIN AF: 0.000199

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000388

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00754 AC: 2016 AN: 267246 Hom.: 0 Cov.: 5 AF XY: 0.00761 AC XY: 1014 AN XY: 133232

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

African (AFR) AF: 0.00834 AC: 59 AN: 7078

American (AMR) AF: 0.00575 AC: 34 AN: 5916

Ashkenazi Jewish (ASJ) AF: 0.00531 AC: 42 AN: 7916

East Asian (EAS) AF: 0.00799 AC: 144 AN: 18030

South Asian (SAS) AF: 0.00674 AC: 22 AN: 3266

European-Finnish (FIN) AF: 0.00628 AC: 159 AN: 25300

Middle Eastern (MID) AF: 0.00609 AC: 7 AN: 1150

European-Non Finnish (NFE) AF: 0.00779 AC: 1429 AN: 183540

Other (OTH) AF: 0.00797 AC: 120 AN: 15050

⚠️ 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: 0.000254 AC: 38 AN: 149364 Hom.: 1 Cov.: 31 AF XY: 0.000220 AC XY: 16 AN XY: 72802

African (AFR) AF: 0.000147 AC: 6 AN: 40876

American (AMR) AF: 0.00 AC: 0 AN: 14912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5096

South Asian (SAS) AF: 0.000640 AC: 3 AN: 4690

European-Finnish (FIN) AF: 0.000199 AC: 2 AN: 10036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000388 AC: 26 AN: 67050

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.00 Hom.: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9
Mutation Taster		=99/1	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: rs111818075; hg19: chr20-464448;