6-31666833-T-G

Variant names:

• chr6-31666833-T-G
• NM_001320.7:c.2T>G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Moderate PM2 PP5_Moderate

The NM_001320.7(CSNK2B):​c.2T>G​(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CSNK2B NM_001320.7 start_lost
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.16

Genes affected

CSNK2B (HGNC:2460): (casein kinase 2 beta) This gene encodes the beta subunit of casein kinase II, a ubiquitous protein kinase which regulates metabolic pathways, signal transduction, transcription, translation, and replication. The enzyme is composed of three subunits, alpha, alpha prime and beta, which form a tetrameric holoenzyme. The alpha and alpha prime subunits are catalytic, while the beta subunit serves regulatory functions. The enzyme localizes to the endoplasmic reticulum and the Golgi apparatus. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ENSG00000263020 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 1 pathogenic variants. Next in-frame start position is after 52 codons. Genomic position: 31667949. Lost 0.238 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-31666833-T-G is Pathogenic according to our data. Variant chr6-31666833-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 1254603.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK2B	NM_001320.7	c.2T>G	p.Met1?	start_lost	Exon 2 of 7	ENST00000375882.7	NP_001311.3
CSNK2B	NM_001282385.2	c.2T>G	p.Met1?	start_lost	Exon 2 of 7		NP_001269314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK2B	ENST00000375882.7	c.2T>G	p.Met1?	start_lost	Exon 2 of 7	1	NM_001320.7	ENSP00000365042.3
ENSG00000263020	ENST00000375880.6	c.2T>G	p.Met1?	start_lost	Exon 2 of 8	3		ENSP00000365040.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000219 AC: 32 AN: 1460032 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 726234

Gnomad4 AFR exome AF: 0.0000599

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000261

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Jul 12, 2021

GeneDx

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Initiation codon variant in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.44
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	.;T;T;T;.;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T;.;.;D;D;D
M_CAP	Benign	0.079	D
MetaRNN	Pathogenic	0.96	D;D;D;D;D;D
MetaSVM	Benign	-0.31	T
PROVEAN	Benign	-2.0	N;N;N;N;N;.
REVEL	Uncertain	0.50
Sift	Benign	0.28	T;D;D;D;D;.
Sift4G	Benign	0.62	T;D;D;D;D;D
Polyphen		1.0	.;D;D;D;.;.
Vest4		0.72
MutPred		0.99		.;Gain of solvent accessibility (P = 0.11);Gain of solvent accessibility (P = 0.11);Gain of solvent accessibility (P = 0.11);Gain of solvent accessibility (P = 0.11);Gain of solvent accessibility (P = 0.11);
MVP		0.82
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.77
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-31634610;