dbSNP rs1463198460: CDK18:p.Arg112Thr (chr1-205523687-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_212503.3(CDK18):c.335G>C(p.Arg112Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000886 in 1,353,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

CDK18
NM_212503.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.668

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07751706).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_212503.3. 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.273+62G>C		intron	N/A	NP_997667.1	Q07002-2
CDK18	NM_212503.3		c.335G>C	p.Arg112Thr	missense	Exon 3 of 16	NP_997668.1	Q07002-3
CDK18	NM_002596.4		c.273+62G>C		intron	N/A	NP_002587.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDK18	ENST00000506784.5	TSL:1	c.335G>C	p.Arg112Thr	missense	Exon 3 of 16	ENSP00000423665.1	Q07002-3
CDK18	ENST00000429964.7	TSL:1 MANE Select	c.273+62G>C		intron	N/A	ENSP00000399082.2	Q07002-2
CDK18	ENST00000360066.6	TSL:1	c.273+62G>C		intron	N/A	ENSP00000353176.2	Q07002-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000160

AC:

AN:

125358

AF XY:

0.00

show subpopulations

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:

0.0000400

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000886

AC:

AN:

1353766

Hom.:

Cov.:

AF XY:

0.00000755

AC XY:

AN XY:

662310

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30082

American (AMR)

AF:

0.00

AC:

AN:

28372

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22962

East Asian (EAS)

AF:

0.00

AC:

AN:

35170

South Asian (SAS)

AF:

0.00

AC:

AN:

73516

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5520

European-Non Finnish (NFE)

AF:

0.0000114

AC:

AN:

1053760

Other (OTH)

AF:

0.00

AC:

AN:

55928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000764

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.32

CADD

Benign

6.0

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.031

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.50

M_CAP

Benign

0.014

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.1

PhyloP100

0.67

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.73

REVEL

Benign

0.068

Sift

Benign

0.060

Sift4G

Benign

0.24

Polyphen

0.0030

Vest4

0.31

MutPred

0.40

Loss of MoRF binding (P = 0.0131)

MVP

0.32

MPC

0.31

ClinPred

0.45

GERP RS

-0.20

gMVP

0.33

Mutation Taster

=97/3

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over