20-478765-CAAAAAAAA-CAAAAAAAAAAAAAA

Variant names:

• chr20-478765-C-CAAAAAA
• rs750062577
• NM_177559.3:c.*5190_*5195dupTTTTTT

Variant summary

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

The ENST00000400227.8(CSNK2A1):​c.1061-11_1061-6dupTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000455 in 175,856 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), 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 0.000053 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000032 (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: 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.*5190_*5195dupTTTTTT		3_prime_UTR	Exon 14 of 14	NP_808227.1	P68400-1
	CSNK2A1	NM_001895.4		c.*5190_*5195dupTTTTTT		3_prime_UTR	Exon 13 of 13	NP_001886.1	P68400-1
	CSNK2A1	NM_177560.3		c.*5190_*5195dupTTTTTT		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.*5190_*5195dupTTTTTT		3_prime_UTR	Exon 14 of 14	ENSP00000217244.3	P68400-1
	CSNK2A1	ENST00000400227.8	TSL:1	c.1061-11_1061-6dupTTTTTT		splice_region intron	N/A	ENSP00000383086.3	E7EU96
	CSNK2A1	ENST00000646561.1		c.*5190_*5195dupTTTTTT		3_prime_UTR	Exon 13 of 13	ENSP00000496569.1	P68400-1

Frequencies

GnomAD3 genomes AF: 0.0000527 AC: 6 AN: 113954 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000191

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000323 AC: 2 AN: 61902 Hom.: 0 Cov.: 0 AF XY: 0.0000548 AC XY: 2 AN XY: 36466

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: 1098

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

South Asian (SAS) AF: 0.0000554 AC: 1 AN: 18038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3848

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 1 AN: 33968

Other (OTH) AF: 0.00 AC: 0 AN: 2706

GnomAD4 genome AF: 0.0000527 AC: 6 AN: 113954 Hom.: 0 Cov.: 27 AF XY: 0.0000922 AC XY: 5 AN XY: 54230

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

African (AFR) AF: 0.000191 AC: 6 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: 0.00 AC: 0 AN: 6116

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52164

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00169570), which strongly suggests a high chance of mosaicism in these individuals.

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

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;