dbSNP rs201468269: CDK18:p.Thr106Lys (chr1-205523669-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_212503.3(CDK18):c.317C>A(p.Thr106Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000646 in 1,393,310 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. 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. T106M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000065 ( 0 hom. )

Consequence

CDK18
NM_212503.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.48

Publications

2 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040991038).

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+44C>A		intron	N/A	NP_997667.1	Q07002-2
CDK18	NM_212503.3		c.317C>A	p.Thr106Lys	missense	Exon 3 of 16	NP_997668.1	Q07002-3
CDK18	NM_002596.4		c.273+44C>A		intron	N/A	NP_002587.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDK18	ENST00000506784.5	TSL:1	c.317C>A	p.Thr106Lys	missense	Exon 3 of 16	ENSP00000423665.1	Q07002-3
CDK18	ENST00000429964.7	TSL:1 MANE Select	c.273+44C>A		intron	N/A	ENSP00000399082.2	Q07002-2
CDK18	ENST00000360066.6	TSL:1	c.273+44C>A		intron	N/A	ENSP00000353176.2	Q07002-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000646

AC:

AN:

1393310

Hom.:

Cov.:

AF XY:

0.00000437

AC XY:

AN XY:

686820

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31500

American (AMR)

AF:

0.00

AC:

AN:

34402

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24654

East Asian (EAS)

AF:

0.00

AC:

AN:

36018

South Asian (SAS)

AF:

0.00

AC:

AN:

78096

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49150

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.00000836

AC:

AN:

1076126

Other (OTH)

AF:

0.00

AC:

AN:

57702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.050

(source)

DANN

Benign

0.20

DEOGEN2

Benign

0.0093

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.40

M_CAP

Benign

0.011

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.92

PhyloP100

-1.5

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.010

REVEL

Benign

0.020

Sift

Benign

1.0

Sift4G

Benign

0.95

Polyphen

0.020

Vest4

0.090

MutPred

0.39

Gain of methylation at T106 (P = 0.0037)

MVP

0.20

MPC

0.25

ClinPred

0.093

GERP RS

-8.1

gMVP

0.19

Mutation Taster

=94/6

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

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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