chr19-1979015-A-C

Position:

• chr19-1979015-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001319.7(CSNK1G2):​c.604A>C​(p.Lys202Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CSNK1G2 NM_001319.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.92

Genes affected

CSNK1G2 (HGNC:2455): (casein kinase 1 gamma 2) Enables protein serine/threonine kinase activity. Involved in peptidyl-serine phosphorylation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSNK1G2	NM_001319.7	c.604A>C	p.Lys202Gln	missense_variant	6/12	ENST00000255641.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSNK1G2	ENST00000255641.13	c.604A>C	p.Lys202Gln	missense_variant	6/12	1	NM_001319.7	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 07, 2022

The c.604A>C (p.K202Q) alteration is located in exon 6 (coding exon 5) of the CSNK1G2 gene. This alteration results from a A to C substitution at nucleotide position 604, causing the lysine (K) at amino acid position 202 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Pathogenic	27
DANN	Benign	0.97
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.076
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.61	N
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.26
Sift	Benign	0.37	T
Sift4G	Benign	1.0	T
Polyphen		0.53	P
Vest4		0.65
MutPred		0.45		Loss of methylation at K202 (P = 0.0067);
MVP		0.52
MPC		1.9
ClinPred		0.92	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.74
gMVP		0.81

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: chr19-1979014;