16-58165766-C-T

Variant names:

• chr16-58165766-C-T
• rs2242444
• NM_001896.4:c.828-58G>A

Variant summary

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

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.60
• Publications: 8 publications found

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]

ACMG classification

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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK2A2	NM_001896.4	c.828-58G>A		intron_variant	Intron 9 of 11	ENST00000262506.8	NP_001887.1
CSNK2A2	XM_047433626.1	c.828-58G>A		intron_variant	Intron 9 of 10		XP_047289582.1
CSNK2A2	XM_017022945.2	c.504-58G>A		intron_variant	Intron 5 of 7		XP_016878434.1
CSNK2A2	XM_005255801.4	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	c.828-58G>A		intron_variant	Intron 9 of 11	1	NM_001896.4	ENSP00000262506.3

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35450 AN: 152012 Hom.: 4667 Cov.: 33

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

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

GnomAD4 genome AF: 0.233 AC: 35490 AN: 152130 Hom.: 4677 Cov.: 33 AF XY: 0.236 AC XY: 17570 AN XY: 74372

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: 42 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11509 AN: 68012

Other (OTH) AF: 0.204 AC: 430 AN: 2108

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

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
DANN	Benign	0.80
PhyloP100		-1.6
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: rs2242444; hg19: chr16-58199670; COSMIC: COSV52641383;