1-205523593-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_212502.3(CDK18):​c.241C>T​(p.Arg81Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000568 in 1,585,474 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000043 ( 1 hom. )

Consequence

CDK18
NM_212502.3 missense

Scores

1
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09961355).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDK18NM_212502.3 linkc.241C>T p.Arg81Trp missense_variant Exon 3 of 16 ENST00000429964.7 NP_997667.1 Q07002-2A0A024R996Q59G02

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDK18ENST00000429964.7 linkc.241C>T p.Arg81Trp missense_variant Exon 3 of 16 1 NM_212502.3 ENSP00000399082.2 Q07002-2

Frequencies

GnomAD3 genomes
AF:
0.000191
AC:
29
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000579
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000123
AC:
24
AN:
195104
Hom.:
1
AF XY:
0.000133
AC XY:
14
AN XY:
105360
show subpopulations
Gnomad AFR exome
AF:
0.000535
Gnomad AMR exome
AF:
0.000518
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000679
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000239
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000426
AC:
61
AN:
1433144
Hom.:
1
Cov.:
33
AF XY:
0.0000493
AC XY:
35
AN XY:
710300
show subpopulations
Gnomad4 AFR exome
AF:
0.000304
Gnomad4 AMR exome
AF:
0.000322
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000261
Gnomad4 SAS exome
AF:
0.0000122
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000319
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.000190
AC:
29
AN:
152330
Hom.:
0
Cov.:
32
AF XY:
0.000215
AC XY:
16
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.000577
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.000204
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00137
AC:
6
ESP6500EA
AF:
0.000117
AC:
1
ExAC
AF:
0.0000666
AC:
8

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 20, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.241C>T (p.R81W) alteration is located in exon 3 (coding exon 2) of the CDK18 gene. This alteration results from a C to T substitution at nucleotide position 241, causing the arginine (R) at amino acid position 81 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.12
.;.;.;T;T
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Benign
0.84
.;T;T;T;T
M_CAP
Uncertain
0.18
D
MetaRNN
Benign
0.10
T;T;T;T;T
MetaSVM
Benign
-0.42
T
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-2.2
N;N;N;N;N
REVEL
Benign
0.17
Sift
Uncertain
0.0070
D;D;D;D;D
Sift4G
Uncertain
0.0060
D;D;D;T;D
Polyphen
1.0
.;D;.;.;.
Vest4
0.50
MVP
0.89
MPC
0.62
ClinPred
0.11
T
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs370210105; hg19: chr1-205492721; API