Genetic Variant CSNK2A1:c.101+86G>A (chr20-508365-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.207

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK2A1	NM_177559.3 link	c.101+86G>A		intron_variant	Intron 3 of 13	ENST00000217244.9	NP_808227.1	P68400-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK2A1	ENST00000217244.9 link	c.101+86G>A		intron_variant	Intron 3 of 13	1	NM_177559.3	ENSP00000217244.3		P68400-1

Frequencies

GnomAD3 genomes

AF:

0.0262

AC:

3991

AN:

152130

Hom.:

131

Cov.:

show subpopulations

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.:

AF XY:

0.00621

AC XY:

4015

AN XY:

646154

show subpopulations

Gnomad4 AFR exome

AF:

0.0772

Gnomad4 AMR exome

AF:

0.0128

Gnomad4 ASJ exome

AF:

0.0172

Gnomad4 EAS exome

AF:

0.0786

Gnomad4 SAS exome

AF:

0.00232

Gnomad4 FIN exome

AF:

0.0110

Gnomad4 NFE exome

AF:

0.00117

Gnomad4 OTH exome

AF:

0.0136

GnomAD4 genome

AF:

0.0263

AC:

4007

AN:

152248

Hom.:

135

Cov.:

AF XY:

0.0262

AC XY:

1953

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0723

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.0850

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.0116

Gnomad4 NFE

AF:

0.00185

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.0146

Hom.:

Bravo

AF:

0.0288

Asia WGS

AF:

0.0430

AC:

149

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.5

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over