1-205523669-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_212503.3(CDK18):​c.317C>T​(p.Thr106Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000324 in 1,545,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

CDK18
NM_212503.3 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.48
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.017926872).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDK18NM_212502.3 linkc.273+44C>T intron_variant Intron 3 of 15 ENST00000429964.7 NP_997667.1 Q07002-2A0A024R996Q59G02

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDK18ENST00000429964.7 linkc.273+44C>T intron_variant Intron 3 of 15 1 NM_212502.3 ENSP00000399082.2 Q07002-2

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152212
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000386
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000468
AC:
7
AN:
149690
Hom.:
0
AF XY:
0.0000254
AC XY:
2
AN XY:
78878
show subpopulations
Gnomad AFR exome
AF:
0.000580
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000900
Gnomad SAS exome
AF:
0.0000469
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000237
AC:
33
AN:
1393312
Hom.:
0
Cov.:
34
AF XY:
0.0000175
AC XY:
12
AN XY:
686822
show subpopulations
Gnomad4 AFR exome
AF:
0.000603
Gnomad4 AMR exome
AF:
0.0000581
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000111
Gnomad4 SAS exome
AF:
0.0000384
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000279
Gnomad4 OTH exome
AF:
0.0000173
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152212
Hom.:
0
Cov.:
33
AF XY:
0.0000807
AC XY:
6
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.000386
Gnomad4 AMR
AF:
0.00
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:
0.0000194
Hom.:
0
Bravo
AF:
0.000185
ESP6500AA
AF:
0.00116
AC:
5
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000474
AC:
5

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 16, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.317C>T (p.T106M) 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 317, causing the threonine (T) at amino acid position 106 to be replaced by a methionine (M). 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
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
0.17
DANN
Benign
0.65
DEOGEN2
Benign
0.0067
.;T;T;T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0025
N
LIST_S2
Benign
0.48
T;T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.018
T;T;T;T
MetaSVM
Benign
-0.99
T
PrimateAI
Benign
0.41
T
PROVEAN
Benign
0.060
N;N;N;N
REVEL
Benign
0.011
Sift
Benign
0.11
T;T;D;T
Sift4G
Benign
0.13
T;T;T;T
Polyphen
0.0030
B;.;.;.
Vest4
0.12
MVP
0.21
MPC
0.21
ClinPred
0.072
T
GERP RS
-8.1
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs201468269; hg19: chr1-205492797; API