20-478765-CAAAAAAAA-C

Variant names:

• chr20-478765-CAAAAAAAA-C
• rs750062577
• NM_177559.3:c.*5188_*5195delTTTTTTTT

Variant summary

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

The ENST00000400227.8(CSNK2A1):​c.1061-13_1061-6delTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 175,854 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00044 (0 hom.)
• Consequence: CSNK2A1 ENST00000400227.8 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.725
• 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.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000237 (27/113954) while in subpopulation NFE AF = 0.000211 (11/52164). AF 95% confidence interval is 0.000118. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High AC in GnomAd4 at 27 AD gene.

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.*5188_*5195delTTTTTTTT		3_prime_UTR	Exon 14 of 14	NP_808227.1	P68400-1
	CSNK2A1	NM_001895.4		c.*5188_*5195delTTTTTTTT		3_prime_UTR	Exon 13 of 13	NP_001886.1	P68400-1
	CSNK2A1	NM_177560.3		c.*5188_*5195delTTTTTTTT		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.*5188_*5195delTTTTTTTT		3_prime_UTR	Exon 14 of 14	ENSP00000217244.3	P68400-1
	CSNK2A1	ENST00000400227.8	TSL:1	c.1061-13_1061-6delTTTTTTTT		splice_region intron	N/A	ENSP00000383086.3	E7EU96
	CSNK2A1	ENST00000646561.1		c.*5188_*5195delTTTTTTTT		3_prime_UTR	Exon 13 of 13	ENSP00000496569.1	P68400-1

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 27 AN: 113954 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000636

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00229

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000211

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000436 AC: 27 AN: 61900 Hom.: 0 AF XY: 0.000274 AC XY: 10 AN XY: 36464

African (AFR) AF: 0.00 AC: 0 AN: 316

American (AMR) AF: 0.00 AC: 0 AN: 1420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1096

East Asian (EAS) AF: 0.00 AC: 0 AN: 330

South Asian (SAS) AF: 0.00 AC: 0 AN: 18038

European-Finnish (FIN) AF: 0.00390 AC: 15 AN: 3848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 178

European-Non Finnish (NFE) AF: 0.000294 AC: 10 AN: 33968

Other (OTH) AF: 0.000739 AC: 2 AN: 2706

GnomAD4 genome AF: 0.000237 AC: 27 AN: 113954 Hom.: 0 Cov.: 27 AF XY: 0.000240 AC XY: 13 AN XY: 54230

African (AFR) AF: 0.0000636 AC: 2 AN: 31462

American (AMR) AF: 0.00 AC: 0 AN: 11360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2754

East Asian (EAS) AF: 0.00 AC: 0 AN: 4094

South Asian (SAS) AF: 0.00 AC: 0 AN: 3524

European-Finnish (FIN) AF: 0.00229 AC: 14 AN: 6116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.000211 AC: 11 AN: 52164

Other (OTH) AF: 0.00 AC: 0 AN: 1508

Alfa AF: 0.00 Hom.: 8

Bravo AF: 0.000106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.72

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;