chr16-58166713-A-C

Variant names:

• chr16-58166713-A-C
• rs58415199
• NM_001896.4:c.727-29T>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001896.4(CSNK2A2):​c.727-29T>G variant causes a intron change. The variant allele was found at a frequency of 0.0809 in 1,514,358 control chromosomes in the GnomAD database, including 6,137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.070 (470 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5667 hom.)
• Consequence: CSNK2A2 NM_001896.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.07
• Publications: 7 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 -18 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.19).
• BP6: Variant 16-58166713-A-C is Benign according to our data. Variant chr16-58166713-A-C is described in ClinVar as Benign. ClinVar VariationId is 1244609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001896.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK2A2	NM_001896.4	MANE Select	c.727-29T>G		intron	N/A	NP_001887.1	P19784

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK2A2	ENST00000262506.8	TSL:1 MANE Select	c.727-29T>G		intron	N/A	ENSP00000262506.3	P19784
	CSNK2A2	ENST00000952604.1		c.766-29T>G		intron	N/A	ENSP00000622663.1
	CSNK2A2	ENST00000931140.1		c.727-29T>G		intron	N/A	ENSP00000601199.1

Frequencies

GnomAD3 genomes AF: 0.0699 AC: 10626 AN: 152044 Hom.: 464 Cov.: 32

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0483

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0567

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0709

Gnomad OTH AF: 0.0627

GnomAD2 exomes AF: 0.0874 AC: 21829 AN: 249684 AF XY: 0.0934

Gnomad AFR exome AF: 0.0539

Gnomad AMR exome AF: 0.0493

Gnomad ASJ exome AF: 0.0599

Gnomad EAS exome AF: 0.163

Gnomad FIN exome AF: 0.0531

Gnomad NFE exome AF: 0.0684

Gnomad OTH exome AF: 0.0722

GnomAD4 exome AF: 0.0821 AC: 111818 AN: 1362196 Hom.: 5667 Cov.: 21 AF XY: 0.0863 AC XY: 59016 AN XY: 683900

African (AFR) AF: 0.0541 AC: 1707 AN: 31558

American (AMR) AF: 0.0508 AC: 2264 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.0628 AC: 1599 AN: 25456

East Asian (EAS) AF: 0.160 AC: 6281 AN: 39218

South Asian (SAS) AF: 0.201 AC: 16942 AN: 84282

European-Finnish (FIN) AF: 0.0514 AC: 2670 AN: 51960

Middle Eastern (MID) AF: 0.0599 AC: 334 AN: 5576

European-Non Finnish (NFE) AF: 0.0739 AC: 75509 AN: 1022416

Other (OTH) AF: 0.0790 AC: 4512 AN: 57130

GnomAD4 genome AF: 0.0700 AC: 10646 AN: 152162 Hom.: 470 Cov.: 32 AF XY: 0.0714 AC XY: 5310 AN XY: 74402

African (AFR) AF: 0.0549 AC: 2279 AN: 41506

American (AMR) AF: 0.0484 AC: 740 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0573 AC: 199 AN: 3470

East Asian (EAS) AF: 0.163 AC: 846 AN: 5176

South Asian (SAS) AF: 0.205 AC: 986 AN: 4820

European-Finnish (FIN) AF: 0.0567 AC: 601 AN: 10598

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0709 AC: 4820 AN: 67992

Other (OTH) AF: 0.0692 AC: 146 AN: 2110

Alfa AF: 0.0650 Hom.: 111

Bravo AF: 0.0667

Asia WGS AF: 0.172 AC: 597 AN: 3478

ClinVar

ClinVar submissions

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	-0.19
CADD	Benign	20
DANN	Benign	0.77
PhyloP100		6.1
BranchPoint Hunter		3.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs58415199; hg19: chr16-58200617; COSMIC: COSV52641402;