1-205523629-A-T

Variant names:

• chr1-205523629-A-T
• ENST00000506784.5:c.277A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_212503.3(CDK18):​c.277A>T​(p.Arg93Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDK18 NM_212503.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.47

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34666628).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK18	NM_212502.3	c.273+4A>T		splice_region_variant, 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+4A>T		splice_region_variant, intron_variant	Intron 3 of 15	1	NM_212502.3	ENSP00000399082.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.277A>T (p.R93W) alteration is located in exon 3 (coding exon 2) of the CDK18 gene. This alteration results from a A to T substitution at nucleotide position 277, causing the arginine (R) at amino acid position 93 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
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	.;T;T;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.71	T;T;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.35	T;T;T;T
MetaSVM	Benign	-0.56	T
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.92	N;N;D;N
REVEL	Benign	0.082
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.014	D;D;D;D
Polyphen		0.84	P;.;.;.
Vest4		0.47
MutPred		0.48		Loss of disorder (P = 0.0055);.;.;Loss of disorder (P = 0.0055);
MVP		0.71
MPC		0.35
ClinPred		1.0	D
GERP RS		4.6
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-205492757;