chr20-483804-A-ATT

Variant names:

• chr20-483804-A-ATT
• rs111818075
• NM_177559.3:c.*155_*156dupAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_177559.3(CSNK2A1):​c.*155_*156dupAA variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0000182 in 274,172 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: CSNK2A1 NM_177559.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.86
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177559.3. 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.*155_*156dupAA		3_prime_UTR	Exon 14 of 14	NP_808227.1	P68400-1
	CSNK2A1	NM_001895.4		c.*155_*156dupAA		3_prime_UTR	Exon 13 of 13	NP_001886.1	P68400-1
	CSNK2A1	NM_177560.3		c.*155_*156dupAA		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.*155_*156dupAA		3_prime_UTR	Exon 14 of 14	ENSP00000217244.3	P68400-1
	CSNK2A1	ENST00000349736.10	TSL:1	c.*155_*156dupAA		3_prime_UTR	Exon 12 of 12	ENSP00000339247.6	P68400-2
	CSNK2A1	ENST00000400227.8	TSL:1	c.1060+2570_1060+2571dupAA		intron	N/A	ENSP00000383086.3	E7EU96

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000182 AC: 5 AN: 274172 Hom.: 0 Cov.: 5 AF XY: 0.0000146 AC XY: 2 AN XY: 136832

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

African (AFR) AF: 0.00 AC: 0 AN: 7234

American (AMR) AF: 0.00 AC: 0 AN: 6092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8106

East Asian (EAS) AF: 0.00 AC: 0 AN: 18580

South Asian (SAS) AF: 0.00 AC: 0 AN: 3340

European-Finnish (FIN) AF: 0.0000387 AC: 1 AN: 25844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1190

European-Non Finnish (NFE) AF: 0.0000212 AC: 4 AN: 188260

Other (OTH) AF: 0.00 AC: 0 AN: 15526

⚠️ 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 Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9

Splicing

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

Other links and lift over

dbSNP: rs111818075; hg19: chr20-464448;