20-483959-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_177559.3(CSNK2A1):c.*2G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000647 in 1,610,634 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00064 (1 hom.)
• Consequence: CSNK2A1 NM_177559.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.727

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 20-483959-C-T is Benign according to our data. Variant chr20-483959-C-T is described in ClinVar as [Benign]. Clinvar id is 1249520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000696 (106/152210) while in subpopulation NFE AF= 0.000632 (43/68030). AF 95% confidence interval is 0.000482. There are 0 homozygotes in gnomad4. There are 45 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 106 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSNK2A1	NM_177559.3	c.*2G>A		3_prime_UTR_variant	14/14	ENST00000217244.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSNK2A1	ENST00000217244.9	c.*2G>A		3_prime_UTR_variant	14/14	1	NM_177559.3	P1

Frequencies

GnomAD3 genomes AF: 0.000696 AC: 106 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000964 AC: 239 AN: 247888 Hom.: 0 AF XY: 0.000924 AC XY: 124 AN XY: 134212

Gnomad AFR exome AF: 0.000191

Gnomad AMR exome AF: 0.000438

Gnomad ASJ exome AF: 0.0141

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0000330

Gnomad FIN exome AF: 0.0000928

Gnomad NFE exome AF: 0.000581

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.000642 AC: 936 AN: 1458424 Hom.: 1 Cov.: 30 AF XY: 0.000644 AC XY: 467 AN XY: 725500

Gnomad4 AFR exome AF: 0.0000301

Gnomad4 AMR exome AF: 0.000451

Gnomad4 ASJ exome AF: 0.0155

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.0000699

Gnomad4 FIN exome AF: 0.000262

Gnomad4 NFE exome AF: 0.000376

Gnomad4 OTH exome AF: 0.00113

GnomAD4 genome AF: 0.000696 AC: 106 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.000605 AC XY: 45 AN XY: 74358

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.00232 Hom.: 0

Bravo AF: 0.000771

EpiCase AF: 0.000873

EpiControl AF: 0.000535

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 08, 2019

- -

CSNK2A1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 07, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	13
Dann	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs142948288; hg19: chr20-464603; COSMIC: COSV99424535;