20-508365-C-T

Variant names:

• chr20-508365-C-T
• rs6037828
• NM_177559.3:c.101+86G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_177559.3(CSNK2A1):​c.101+86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00882 in 1,448,086 control chromosomes in the GnomAD database, including 363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (135 hom., cov: 32)
  • Exomes 𝑓: 0.0068 (228 hom.)
• Consequence: CSNK2A1 NM_177559.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.207
• Publications: 3 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, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics, G2P
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 20-508365-C-T is Benign according to our data. Variant chr20-508365-C-T is described in ClinVar as Benign. ClinVar VariationId is 1258016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0785 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK2A1	NM_177559.3	MANE Select	c.101+86G>A		intron	N/A	NP_808227.1
	CSNK2A1	NM_001362770.2		c.101+86G>A		intron	N/A	NP_001349699.1
	CSNK2A1	NM_001362771.2		c.101+86G>A		intron	N/A	NP_001349700.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK2A1	ENST00000217244.9	TSL:1 MANE Select	c.101+86G>A		intron	N/A	ENSP00000217244.3
	CSNK2A1	ENST00000400227.8	TSL:1	c.101+86G>A		intron	N/A	ENSP00000383086.3
	CSNK2A1	ENST00000349736.10	TSL:1	c.-307-3136G>A		intron	N/A	ENSP00000339247.6

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3991 AN: 152130 Hom.: 131 Cov.: 32

Gnomad AFR AF: 0.0720

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0134

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.0854

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00185

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00676 AC: 8762 AN: 1295838 Hom.: 228 Cov.: 17 AF XY: 0.00621 AC XY: 4015 AN XY: 646154

African (AFR) AF: 0.0772 AC: 2285 AN: 29592

American (AMR) AF: 0.0128 AC: 488 AN: 38084

Ashkenazi Jewish (ASJ) AF: 0.0172 AC: 378 AN: 21928

East Asian (EAS) AF: 0.0786 AC: 2952 AN: 37544

South Asian (SAS) AF: 0.00232 AC: 171 AN: 73640

European-Finnish (FIN) AF: 0.0110 AC: 564 AN: 51224

Middle Eastern (MID) AF: 0.00640 AC: 34 AN: 5314

European-Non Finnish (NFE) AF: 0.00117 AC: 1148 AN: 983940

Other (OTH) AF: 0.0136 AC: 742 AN: 54572

GnomAD4 genome AF: 0.0263 AC: 4007 AN: 152248 Hom.: 135 Cov.: 32 AF XY: 0.0262 AC XY: 1953 AN XY: 74428

African (AFR) AF: 0.0723 AC: 3002 AN: 41514

American (AMR) AF: 0.0133 AC: 203 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 51 AN: 3470

East Asian (EAS) AF: 0.0850 AC: 441 AN: 5188

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4828

European-Finnish (FIN) AF: 0.0116 AC: 123 AN: 10596

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00185 AC: 126 AN: 68034

Other (OTH) AF: 0.0152 AC: 32 AN: 2108

Alfa AF: 0.0174 Hom.: 34

Bravo AF: 0.0288

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.45
PhyloP100		-0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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

Other links and lift over

dbSNP: rs6037828; hg19: chr20-489009; COSMIC: COSV53935266; COSMIC: COSV53935266;