rs201468269

Variant names:

• chr1-205523669-C-A
• rs201468269
• ENST00000506784.5:c.317C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-205523669-C-A
• chr1-205523669-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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. 13/18 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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]

ACMG classification

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=0.040991038).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK18	NM_212502.3	c.273+44C>A		intron_variant	Intron 3 of 15	ENST00000429964.7	NP_997667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK18	ENST00000429964.7	c.273+44C>A		intron_variant	Intron 3 of 15	1	NM_212502.3	ENSP00000399082.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000646 AC: 9 AN: 1393310 Hom.: 0 Cov.: 34 AF XY: 0.00000437 AC XY: 3 AN XY: 686820

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000836

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.050
DANN	Benign	0.20
DEOGEN2	Benign	0.0093	.;T;T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.40	T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.041	T;T;T;T
MetaSVM	Benign	-0.92	T
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.010	N;N;N;N
REVEL	Benign	0.020
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.95	T;T;T;T
Polyphen		0.020	B;.;.;.
Vest4		0.090
MutPred		0.39		Gain of methylation at T106 (P = 0.0037);.;.;Gain of methylation at T106 (P = 0.0037);
MVP		0.20
MPC		0.25
ClinPred		0.093	T
GERP RS		-8.1
gMVP		0.19

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

Other links and lift over

dbSNP: rs201468269; hg19: chr1-205492797;