Genetic Variant CSNK2A2:c.828-58G>A (chr16-58165766-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001896.4(CSNK2A2):c.828-58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,554,906 control chromosomes in the GnomAD database, including 29,364 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4677 hom., cov: 33)

Exomes 𝑓: 0.18 ( 24687 hom. )

Consequence

CSNK2A2
NM_001896.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.60

Publications

8 publications found

Variant links:

Genes affected

CSNK2A2 (HGNC:2459): (casein kinase 2 alpha 2) This gene encodes the alpha', or alpha 2, catalytic subunit of the protein kinase enzyme, casein kinase 2 (CK2). Casein kinase 2 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 rhythms. This heterotetrameric kinase includes two catalytic subunits, either alpha or alpha', and two regulatory beta subunits. The closely related gene paralog encoding the alpha, or alpha 1 subunit (CSNK2A1, Gene ID: 1457) is found on chromosome 20. An intronic variant in this gene (alpha 2) may be associated with leukocyte telomere length in a South Asian population. A related transcribed pseudogene is found on chromosome 11. [provided by RefSeq, Aug 2017]

CSNK2A2 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 16-58165766-C-T is Benign according to our data. Variant chr16-58165766-C-T is described in ClinVar as Benign. ClinVar VariationId is 1280045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CSNK2A2	NM_001896.4 link	c.828-58G>A	intron_variant	Intron 9 of 11	ENST00000262506.8	NP_001887.1	P19784
CSNK2A2	XM_047433626.1 link	c.828-58G>A	intron_variant	Intron 9 of 10		XP_047289582.1
CSNK2A2	XM_017022945.2 link	c.504-58G>A	intron_variant	Intron 5 of 7		XP_016878434.1
CSNK2A2	XM_005255801.4 link	c.417-58G>A	intron_variant	Intron 8 of 10		XP_005255858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK2A2	ENST00000262506.8 link	c.828-58G>A		intron_variant	Intron 9 of 11	1	NM_001896.4	ENSP00000262506.3		P19784

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35450

AN:

152012

Hom.:

4667

Cov.:

show subpopulations

Gnomad AFR

AF:

0.334

Gnomad AMI

AF:

0.243

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.208

GnomAD4 exome

AF:

0.181

AC:

253423

AN:

1402776

Hom.:

24687

AF XY:

0.177

AC XY:

123132

AN XY:

695598

show subpopulations

African (AFR)

AF:

0.348

AC:

10972

AN:

31516

American (AMR)

AF:

0.367

AC:

13830

AN:

37670

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

3597

AN:

22936

East Asian (EAS)

AF:

0.159

AC:

6248

AN:

39198

South Asian (SAS)

AF:

0.122

AC:

9460

AN:

77390

European-Finnish (FIN)

AF:

0.269

AC:

13894

AN:

51668

Middle Eastern (MID)

AF:

0.151

AC:

834

AN:

5510

European-Non Finnish (NFE)

AF:

0.170

AC:

183961

AN:

1079038

Other (OTH)

AF:

0.184

AC:

10627

AN:

57850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

9830

19661

29491

39322

49152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6748

13496

20244

26992

33740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.233

AC:

35490

AN:

152130

Hom.:

4677

Cov.:

AF XY:

0.236

AC XY:

17570

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.334

AC:

13832

AN:

41462

American (AMR)

AF:

0.309

AC:

4719

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

574

AN:

3470

East Asian (EAS)

AF:

0.131

AC:

680

AN:

5186

South Asian (SAS)

AF:

0.120

AC:

578

AN:

4828

European-Finnish (FIN)

AF:

0.275

AC:

2904

AN:

10564

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.169

AC:

11509

AN:

68012

Other (OTH)

AF:

0.204

AC:

430

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1363

2725

4088

5450

6813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

358

716

1074

1432

1790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.206

Hom.:

567

Bravo

AF:

0.242

Asia WGS

AF:

0.152

AC:

530

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

- -

Nov 10, 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

-0.88

CADD

Benign

1.4

(source)

DANN

Benign

0.80

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over