20-478765-CAAAAAAAA-CAAAAAAA

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000400227.8(CSNK2A1):​c.1061-6delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0060 (1 hom., cov: 27)
  • Exomes 𝑓: 0.26 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Uncertain_significance. The variant received 0 ACMG points.

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

Frequencies

GnomAD3 genomes AF: 0.00593 AC: 676 AN: 113926 Hom.: 1 Cov.: 27

Gnomad AFR AF: 0.00801

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00361

Gnomad ASJ AF: 0.000363

Gnomad EAS AF: 0.00122

Gnomad SAS AF: 0.00170

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0115

Gnomad NFE AF: 0.00336

Gnomad OTH AF: 0.00729

GnomAD2 exomes AF: 0.311 AC: 489 AN: 1572 AF XY: 0.319

Gnomad AFR exome AF: 0.375

Gnomad AMR exome AF: 0.305

Gnomad ASJ exome AF: 0.450

Gnomad EAS exome AF: 0.286

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.301

Gnomad OTH exome AF: 0.345

GnomAD4 exome AF: 0.260 AC: 15951 AN: 61318 Hom.: 0 Cov.: 0 AF XY: 0.260 AC XY: 9400 AN XY: 36096

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

African (AFR) AF: 0.217 AC: 68 AN: 314

American (AMR) AF: 0.240 AC: 339 AN: 1412

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 278 AN: 1086

East Asian (EAS) AF: 0.212 AC: 70 AN: 330

South Asian (SAS) AF: 0.262 AC: 4670 AN: 17794

European-Finnish (FIN) AF: 0.263 AC: 997 AN: 3798

Middle Eastern (MID) AF: 0.281 AC: 50 AN: 178

European-Non Finnish (NFE) AF: 0.261 AC: 8795 AN: 33712

Other (OTH) AF: 0.254 AC: 684 AN: 2694

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00596 AC: 679 AN: 113904 Hom.: 1 Cov.: 27 AF XY: 0.00629 AC XY: 341 AN XY: 54240

African (AFR) AF: 0.00809 AC: 255 AN: 31506

American (AMR) AF: 0.00361 AC: 41 AN: 11370

Ashkenazi Jewish (ASJ) AF: 0.000363 AC: 1 AN: 2754

East Asian (EAS) AF: 0.00123 AC: 5 AN: 4076

South Asian (SAS) AF: 0.00171 AC: 6 AN: 3500

European-Finnish (FIN) AF: 0.0298 AC: 182 AN: 6104

Middle Eastern (MID) AF: 0.0126 AC: 3 AN: 238

European-Non Finnish (NFE) AF: 0.00336 AC: 175 AN: 52136

Other (OTH) AF: 0.00728 AC: 11 AN: 1512

Alfa AF: 0.00 Hom.: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.068
Mutation Taster		=98/2	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; COSMIC: COSV53938451; COSMIC: COSV53938451;