20-483804-AT-A

Variant names:

• chr20-483804-AT-A
• rs111818075
• NM_177559.3:c.*156delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_177559.3(CSNK2A1):​c.*156delA variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0792 in 149,322 control chromosomes in the GnomAD database, including 504 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.079 (504 hom., cov: 31)
  • Exomes 𝑓: 0.077 (664 hom.)
  • Failed GnomAD Quality Control
• Consequence: CSNK2A1 NM_177559.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.86
• Publications: 1 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 -10 ACMG points.

• BP6: Variant 20-483804-AT-A is Benign according to our data. Variant chr20-483804-AT-A is described in ClinVar as Benign. ClinVar VariationId is 1273190.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

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.*156delA		3_prime_UTR	Exon 14 of 14	NP_808227.1	P68400-1
	CSNK2A1	NM_001895.4		c.*156delA		3_prime_UTR	Exon 13 of 13	NP_001886.1	P68400-1
	CSNK2A1	NM_177560.3		c.*156delA		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.*156delA		3_prime_UTR	Exon 14 of 14	ENSP00000217244.3	P68400-1
	CSNK2A1	ENST00000349736.10	TSL:1	c.*156delA		3_prime_UTR	Exon 12 of 12	ENSP00000339247.6	P68400-2
	CSNK2A1	ENST00000400227.8	TSL:1	c.1060+2571delA		intron	N/A	ENSP00000383086.3	E7EU96

Frequencies

GnomAD3 genomes AF: 0.0790 AC: 11789 AN: 149214 Hom.: 499 Cov.: 31

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.0232

Gnomad AMR AF: 0.0660

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0202

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0694

Gnomad OTH AF: 0.0627

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0767 AC: 20640 AN: 268994 Hom.: 664 Cov.: 5 AF XY: 0.0777 AC XY: 10430 AN XY: 134226

African (AFR) AF: 0.103 AC: 736 AN: 7120

American (AMR) AF: 0.101 AC: 605 AN: 5986

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 968 AN: 7998

East Asian (EAS) AF: 0.0180 AC: 326 AN: 18064

South Asian (SAS) AF: 0.118 AC: 389 AN: 3290

European-Finnish (FIN) AF: 0.104 AC: 2641 AN: 25344

Middle Eastern (MID) AF: 0.0742 AC: 87 AN: 1172

European-Non Finnish (NFE) AF: 0.0733 AC: 13542 AN: 184800

Other (OTH) AF: 0.0884 AC: 1346 AN: 15220

GnomAD4 genome AF: 0.0792 AC: 11824 AN: 149322 Hom.: 504 Cov.: 31 AF XY: 0.0793 AC XY: 5772 AN XY: 72782

African (AFR) AF: 0.0959 AC: 3918 AN: 40860

American (AMR) AF: 0.0665 AC: 991 AN: 14904

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 348 AN: 3442

East Asian (EAS) AF: 0.0204 AC: 104 AN: 5096

South Asian (SAS) AF: 0.134 AC: 629 AN: 4690

European-Finnish (FIN) AF: 0.101 AC: 1017 AN: 10032

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0693 AC: 4647 AN: 67038

Other (OTH) AF: 0.0620 AC: 128 AN: 2064

Alfa AF: 0.0218 Hom.: 17

Bravo AF: 0.0738

Asia WGS AF: 0.0870 AC: 305 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs111818075; hg19: chr20-464448;