20-478765-CAAAAAAAA-CAAAAAAAAA

Variant names:

• chr20-478765-C-CA
• rs750062577
• NM_177559.3:c.*5195dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000400227.8(CSNK2A1):​c.1061-6dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0932 in 175,478 control chromosomes in the GnomAD database, including 840 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (840 hom., cov: 27)
  • Exomes 𝑓: 0.072 (0 hom.)
• Consequence: CSNK2A1 ENST00000400227.8 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000400227.8. 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.*5195dupT		3_prime_UTR	Exon 14 of 14	NP_808227.1	P68400-1
	CSNK2A1	NM_001895.4		c.*5195dupT		3_prime_UTR	Exon 13 of 13	NP_001886.1	P68400-1
	CSNK2A1	NM_177560.3		c.*5195dupT		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.*5195dupT		3_prime_UTR	Exon 14 of 14	ENSP00000217244.3	P68400-1
	CSNK2A1	ENST00000400227.8	TSL:1	c.1061-6dupT		splice_region intron	N/A	ENSP00000383086.3	E7EU96
	CSNK2A1	ENST00000646561.1		c.*5195dupT		3_prime_UTR	Exon 13 of 13	ENSP00000496569.1	P68400-1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 11891 AN: 113896 Hom.: 837 Cov.: 27

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0494

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0512

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.0397

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.0530

Gnomad NFE AF: 0.0503

Gnomad OTH AF: 0.107

GnomAD2 exomes AF: 0.0585 AC: 92 AN: 1572 AF XY: 0.0574

Gnomad AFR exome AF: 0.0313

Gnomad AMR exome AF: 0.0788

Gnomad ASJ exome AF: 0.0500

Gnomad EAS exome AF: 0.0408

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0616

Gnomad OTH exome AF: 0.0345

GnomAD4 exome AF: 0.0723 AC: 4456 AN: 61602 Hom.: 0 Cov.: 0 AF XY: 0.0742 AC XY: 2690 AN XY: 36276

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

African (AFR) AF: 0.108 AC: 34 AN: 314

American (AMR) AF: 0.0938 AC: 133 AN: 1418

Ashkenazi Jewish (ASJ) AF: 0.0641 AC: 70 AN: 1092

East Asian (EAS) AF: 0.0788 AC: 26 AN: 330

South Asian (SAS) AF: 0.0774 AC: 1387 AN: 17922

European-Finnish (FIN) AF: 0.0772 AC: 295 AN: 3820

Middle Eastern (MID) AF: 0.0449 AC: 8 AN: 178

European-Non Finnish (NFE) AF: 0.0677 AC: 2289 AN: 33830

Other (OTH) AF: 0.0793 AC: 214 AN: 2698

⚠️ 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: 0.105 AC: 11906 AN: 113876 Hom.: 840 Cov.: 27 AF XY: 0.105 AC XY: 5687 AN XY: 54224

African (AFR) AF: 0.185 AC: 5832 AN: 31480

American (AMR) AF: 0.174 AC: 1983 AN: 11364

Ashkenazi Jewish (ASJ) AF: 0.0512 AC: 141 AN: 2754

East Asian (EAS) AF: 0.142 AC: 579 AN: 4070

South Asian (SAS) AF: 0.0400 AC: 140 AN: 3500

European-Finnish (FIN) AF: 0.0651 AC: 398 AN: 6118

Middle Eastern (MID) AF: 0.0583 AC: 14 AN: 240

European-Non Finnish (NFE) AF: 0.0503 AC: 2622 AN: 52128

Other (OTH) AF: 0.107 AC: 162 AN: 1514

Alfa AF: 0.00923 Hom.: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.068
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs750062577; hg19: chr20-459409;