NM_001896.4:c.220G>C

Variant names:

• chr16-58186853-C-G
• NM_001896.4:c.220G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001896.4(CSNK2A2):​c.220G>C​(p.Val74Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSNK2A2 NM_001896.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41974175).

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.220G>C	p.Val74Leu	missense	Exon 3 of 12	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.220G>C	p.Val74Leu	missense	Exon 3 of 12	ENSP00000262506.3	P19784
	CSNK2A2	ENST00000952604.1		c.220G>C	p.Val74Leu	missense	Exon 3 of 13	ENSP00000622663.1
	CSNK2A2	ENST00000931140.1		c.220G>C	p.Val74Leu	missense	Exon 3 of 11	ENSP00000601199.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.0051	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.87	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.17
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.057	T
Polyphen		0.031	B
Vest4		0.55
MutPred		0.51		Gain of glycosylation at P73 (P = 0.0954)
MVP		0.41
MPC		1.5
ClinPred		0.89	D
GERP RS		5.6
PromoterAI		-0.0058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.67

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

hg19: chr16-58220757;