1-205523222-C-G

Variant names:

• chr1-205523222-C-G
• rs760625150
• NM_212502.3:c.55C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_212502.3(CDK18):​c.55C>G​(p.Arg19Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R19C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CDK18 NM_212502.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.34
• Publications: 1 publications found

Genes affected

CDK18 (HGNC:8751): (cyclin dependent kinase 18) Predicted to enable ATP binding activity; cyclin-dependent protein serine/threonine kinase activity; and protein serine kinase activity. Predicted to be involved in protein phosphorylation and regulation of transcription involved in G1/S transition of mitotic cell cycle. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27979398).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_212502.3. 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
	CDK18	NM_212502.3	MANE Select	c.55C>G	p.Arg19Gly	missense	Exon 2 of 16	NP_997667.1	Q07002-2
	CDK18	NM_212503.3		c.55C>G	p.Arg19Gly	missense	Exon 2 of 16	NP_997668.1	Q07002-3
	CDK18	NM_002596.4		c.55C>G	p.Arg19Gly	missense	Exon 2 of 16	NP_002587.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK18	ENST00000429964.7	TSL:1 MANE Select	c.55C>G	p.Arg19Gly	missense	Exon 2 of 16	ENSP00000399082.2	Q07002-2
	CDK18	ENST00000506784.5	TSL:1	c.55C>G	p.Arg19Gly	missense	Exon 2 of 16	ENSP00000423665.1	Q07002-3
	CDK18	ENST00000360066.6	TSL:1	c.55C>G	p.Arg19Gly	missense	Exon 2 of 16	ENSP00000353176.2	Q07002-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461370 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727028

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111550

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	23
DANN	Benign	0.91
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.068
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.87	T
PhyloP100		4.3
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.17
Sift	Benign	1.0	T
Sift4G	Benign	0.27	T
Polyphen		0.047	B
Vest4		0.79
MutPred		0.22		Loss of catalytic residue at R19 (P = 0.0414)
MVP		0.74
MPC		0.56
ClinPred		0.93	D
GERP RS		5.0
Varity_R		0.34
gMVP		0.63
Mutation Taster		=27/73	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs760625150; hg19: chr1-205492350;