19-1978706-C-G

Variant names:

• chr19-1978706-C-G
• rs761629089
• NM_001319.7:c.403C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001319.7(CSNK1G2):​c.403C>G​(p.Arg135Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,442,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CSNK1G2 NM_001319.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.16
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.861

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001319.7. 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
	CSNK1G2	NM_001319.7	MANE Select	c.403C>G	p.Arg135Gly	missense	Exon 5 of 12	NP_001310.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK1G2	ENST00000255641.13	TSL:1 MANE Select	c.403C>G	p.Arg135Gly	missense	Exon 5 of 12	ENSP00000255641.7	P78368
	CSNK1G2	ENST00000890345.1		c.403C>G	p.Arg135Gly	missense	Exon 6 of 13	ENSP00000560404.1
	CSNK1G2	ENST00000890346.1		c.403C>G	p.Arg135Gly	missense	Exon 5 of 12	ENSP00000560405.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000435 AC: 1 AN: 230050 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000978

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1442238 Hom.: 0 Cov.: 40 AF XY: 0.00000140 AC XY: 1 AN XY: 716642

African (AFR) AF: 0.00 AC: 0 AN: 32976

American (AMR) AF: 0.00 AC: 0 AN: 43436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25562

East Asian (EAS) AF: 0.00 AC: 0 AN: 38618

South Asian (SAS) AF: 0.00 AC: 0 AN: 84748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1101366

Other (OTH) AF: 0.00 AC: 0 AN: 59340

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

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	0.99
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.2
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-6.4	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.67	P
Vest4		0.78
MutPred		0.73		Loss of solvent accessibility (P = 0.0159)
MVP		0.72
MPC		2.7
ClinPred		0.92	D
GERP RS		4.4
PromoterAI		-0.044	Neutral
Varity_R		0.90
gMVP		0.95
Mutation Taster		=23/77	disease causing

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

Other links and lift over

dbSNP: rs761629089; hg19: chr19-1978705;