20-484053-A-C

Variant names:

• chr20-484053-A-C
• NM_177559.3:c.1084T>G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Moderate BP6_Moderate

The NM_177559.3(CSNK2A1):​c.1084T>G​(p.Ser362Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSNK2A1 NM_177559.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.97

Genes affected

CSNK2A1 (HGNC:2457): (casein kinase 2 alpha 1) Casein kinase II 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 rhythm. The kinase exists as a tetramer and is composed of an alpha, an alpha-prime, and two beta subunits. The alpha subunits contain the catalytic activity while the beta subunits undergo autophosphorylation. The protein encoded by this gene represents the alpha subunit. Multiple transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Apr 2018]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the CSNK2A1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 28 curated pathogenic missense variants (we use a threshold of 10). The gene has 7 curated benign missense variants. Gene score misZ: 3.7123 (above the threshold of 3.09). Trascript score misZ: 5.3205 (above the threshold of 3.09). GenCC associations: The gene is linked to syndromic intellectual disability, Okur-Chung neurodevelopmental syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.117248446).
• BP6: Variant 20-484053-A-C is Benign according to our data. Variant chr20-484053-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1178023.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSNK2A1	NM_177559.3	c.1084T>G	p.Ser362Ala	missense_variant	Exon 14 of 14	ENST00000217244.9	NP_808227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSNK2A1	ENST00000217244.9	c.1084T>G	p.Ser362Ala	missense_variant	Exon 14 of 14	1	NM_177559.3	ENSP00000217244.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 26, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;T;T;.;T;T;.;.;T;.;.;.;.;.;T;T
Eigen	Benign	-0.094
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.78	.;.;.;.;.;.;T;.;.;T;.;T;T;T;.;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.20	N;N;N;.;N;N;.;.;N;.;.;.;.;.;N;N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	0.050	.;.;.;.;N;.;.;.;.;.;.;.;.;.;.;.
REVEL	Benign	0.056
Sift	Benign	0.25	.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.
Sift4G	Benign	0.22	.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.
Polyphen		0.0	B;B;B;.;B;B;.;.;B;.;.;.;.;.;B;B
Vest4		0.14
MutPred		0.15		Loss of glycosylation at S362 (P = 0.0045);Loss of glycosylation at S362 (P = 0.0045);Loss of glycosylation at S362 (P = 0.0045);.;Loss of glycosylation at S362 (P = 0.0045);Loss of glycosylation at S362 (P = 0.0045);.;.;Loss of glycosylation at S362 (P = 0.0045);.;.;.;.;.;Loss of glycosylation at S362 (P = 0.0045);Loss of glycosylation at S362 (P = 0.0045);
MVP		0.68
MPC		0.045
ClinPred		0.43	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.068
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr20-464697;