chr16-58174632-T-C

Position:

• chr16-58174632-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001896.4(CSNK2A2):​c.370-122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0793 in 592,136 control chromosomes in the GnomAD database, including 2,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (478 hom., cov: 32)
  • Exomes 𝑓: 0.083 (1900 hom.)
• Consequence: CSNK2A2 NM_001896.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0110

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-58174632-T-C is Benign according to our data. Variant chr16-58174632-T-C is described in ClinVar as [Benign]. Clinvar id is 1234851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSNK2A2	NM_001896.4	c.370-122A>G		intron_variant		ENST00000262506.8	NP_001887.1
CSNK2A2	XM_047433626.1	c.370-122A>G		intron_variant			XP_047289582.1
CSNK2A2	XM_005255801.4	c.-42-122A>G		intron_variant			XP_005255858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSNK2A2	ENST00000262506.8	c.370-122A>G		intron_variant		1	NM_001896.4	ENSP00000262506.3

Frequencies

GnomAD3 genomes AF: 0.0698 AC: 10618 AN: 152026 Hom.: 472 Cov.: 32

Gnomad AFR AF: 0.0535

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.0595

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0710

Gnomad OTH AF: 0.0632

GnomAD4 exome AF: 0.0826 AC: 36338 AN: 439992 Hom.: 1900 AF XY: 0.0867 AC XY: 20112 AN XY: 232064

Gnomad4 AFR exome AF: 0.0556

Gnomad4 AMR exome AF: 0.0511

Gnomad4 ASJ exome AF: 0.0615

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.188

Gnomad4 FIN exome AF: 0.0553

Gnomad4 NFE exome AF: 0.0736

Gnomad4 OTH exome AF: 0.0712

GnomAD4 genome AF: 0.0699 AC: 10638 AN: 152144 Hom.: 478 Cov.: 32 AF XY: 0.0714 AC XY: 5314 AN XY: 74388

Gnomad4 AFR AF: 0.0536

Gnomad4 AMR AF: 0.0486

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.0595

Gnomad4 NFE AF: 0.0710

Gnomad4 OTH AF: 0.0696

Alfa AF: 0.0668 Hom.: 39

Bravo AF: 0.0663

Asia WGS AF: 0.172 AC: 595 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.4
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs3736397; hg19: chr16-58208536;