dbSNP rs965308424: CDK18:p.Arg87Gly (chr1-205523611-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_212502.3(CDK18):c.259C>G(p.Arg87Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,420,644 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. R87C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CDK18
NM_212502.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.70

Publications

0 publications found

Variant links:

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]

CDK18 links:

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ACMG classification

Classification was made for transcript

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=0.4213625).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDK18	NM_212502.3	MANE Select	c.259C>G	p.Arg87Gly	missense	Exon 3 of 16	NP_997667.1	Q07002-2
CDK18	NM_212503.3		c.259C>G	p.Arg87Gly	missense	Exon 3 of 16	NP_997668.1	Q07002-3
CDK18	NM_002596.4		c.259C>G	p.Arg87Gly	missense	Exon 3 of 16	NP_002587.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDK18	ENST00000429964.7	TSL:1 MANE Select	c.259C>G	p.Arg87Gly	missense	Exon 3 of 16	ENSP00000399082.2	Q07002-2
CDK18	ENST00000506784.5	TSL:1	c.259C>G	p.Arg87Gly	missense	Exon 3 of 16	ENSP00000423665.1	Q07002-3
CDK18	ENST00000360066.6	TSL:1	c.259C>G	p.Arg87Gly	missense	Exon 3 of 16	ENSP00000353176.2	Q07002-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1420644

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

702960

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32620

American (AMR)

AF:

0.00

AC:

AN:

38276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25416

East Asian (EAS)

AF:

0.00

AC:

AN:

37568

South Asian (SAS)

AF:

0.0000124

AC:

AN:

80876

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50010

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

9.16e-7

AC:

AN:

1091366

Other (OTH)

AF:

0.00

AC:

AN:

58786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.42

MetaSVM

Uncertain

-0.080

PhyloP100

4.7

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.19

Sift

Benign

0.11

Sift4G

Benign

0.085

Polyphen

1.0

Vest4

0.63

MutPred

0.20

Loss of MoRF binding (P = 0.0527)

MVP

0.86

MPC

0.83

ClinPred

0.99

GERP RS

5.8

Varity_R

0.56

gMVP

0.67

Mutation Taster

=23/77

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over