20-478765-CAAAAAAAA-CAAAAAAAAAA

Variant names:

• chr20-478765-C-CAA
• rs750062577
• NM_177559.3:c.*5194_*5195dupTT

Variant summary

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

The ENST00000400227.8(CSNK2A1):​c.1061-7_1061-6dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0176 in 175,552 control chromosomes in the GnomAD database, including 77 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.022 (77 hom., cov: 27)
  • Exomes 𝑓: 0.0090 (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 = 0.069 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.*5194_*5195dupTT		3_prime_UTR	Exon 14 of 14	NP_808227.1	P68400-1
	CSNK2A1	NM_001895.4		c.*5194_*5195dupTT		3_prime_UTR	Exon 13 of 13	NP_001886.1	P68400-1
	CSNK2A1	NM_177560.3		c.*5194_*5195dupTT		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.*5194_*5195dupTT		3_prime_UTR	Exon 14 of 14	ENSP00000217244.3	P68400-1
	CSNK2A1	ENST00000400227.8	TSL:1	c.1061-7_1061-6dupTT		splice_region intron	N/A	ENSP00000383086.3	E7EU96
	CSNK2A1	ENST00000646561.1		c.*5194_*5195dupTT		3_prime_UTR	Exon 13 of 13	ENSP00000496569.1	P68400-1

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 2544 AN: 113914 Hom.: 77 Cov.: 27

Gnomad AFR AF: 0.0715

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.0171

Gnomad EAS AF: 0.000733

Gnomad SAS AF: 0.000284

Gnomad FIN AF: 0.000818

Gnomad MID AF: 0.0152

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.0166

GnomAD2 exomes AF: 0.00636 AC: 10 AN: 1572 AF XY: 0.00418

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00362

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00897 AC: 553 AN: 61658 Hom.: 0 Cov.: 0 AF XY: 0.00917 AC XY: 333 AN XY: 36310

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

African (AFR) AF: 0.0353 AC: 11 AN: 312

American (AMR) AF: 0.0156 AC: 22 AN: 1414

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 17 AN: 1092

East Asian (EAS) AF: 0.00305 AC: 1 AN: 328

South Asian (SAS) AF: 0.00919 AC: 165 AN: 17958

European-Finnish (FIN) AF: 0.00548 AC: 21 AN: 3834

Middle Eastern (MID) AF: 0.0225 AC: 4 AN: 178

European-Non Finnish (NFE) AF: 0.00863 AC: 292 AN: 33842

Other (OTH) AF: 0.00741 AC: 20 AN: 2700

⚠️ 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: 0.0223 AC: 2545 AN: 113894 Hom.: 77 Cov.: 27 AF XY: 0.0215 AC XY: 1166 AN XY: 54232

African (AFR) AF: 0.0714 AC: 2249 AN: 31478

American (AMR) AF: 0.0130 AC: 148 AN: 11368

Ashkenazi Jewish (ASJ) AF: 0.0171 AC: 47 AN: 2754

East Asian (EAS) AF: 0.000736 AC: 3 AN: 4076

South Asian (SAS) AF: 0.000286 AC: 1 AN: 3500

European-Finnish (FIN) AF: 0.000818 AC: 5 AN: 6112

Middle Eastern (MID) AF: 0.0167 AC: 4 AN: 240

European-Non Finnish (NFE) AF: 0.00121 AC: 63 AN: 52146

Other (OTH) AF: 0.0165 AC: 25 AN: 1512

Alfa AF: 0.000125 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

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;