1-205523651-G-C

Variant names:

• chr1-205523651-G-C
• rs574552377
• ENST00000506784.5:c.299G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_212503.3(CDK18):​c.299G>C​(p.Arg100Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000713 in 1,402,178 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. R100Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CDK18 NM_212503.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07651213).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK18	NM_212502.3	MANE Select	c.273+26G>C		intron	N/A	NP_997667.1	Q07002-2
	CDK18	NM_212503.3		c.299G>C	p.Arg100Pro	missense	Exon 3 of 16	NP_997668.1	Q07002-3
	CDK18	NM_002596.4		c.273+26G>C		intron	N/A	NP_002587.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK18	ENST00000506784.5	TSL:1	c.299G>C	p.Arg100Pro	missense	Exon 3 of 16	ENSP00000423665.1	Q07002-3
	CDK18	ENST00000429964.7	TSL:1 MANE Select	c.273+26G>C		intron	N/A	ENSP00000399082.2	Q07002-2
	CDK18	ENST00000360066.6	TSL:1	c.273+26G>C		intron	N/A	ENSP00000353176.2	Q07002-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1402178 Hom.: 0 Cov.: 34 AF XY: 0.00000145 AC XY: 1 AN XY: 691982

African (AFR) AF: 0.00 AC: 0 AN: 31902

American (AMR) AF: 0.00 AC: 0 AN: 35694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25056

East Asian (EAS) AF: 0.00 AC: 0 AN: 36390

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080746

Other (OTH) AF: 0.00 AC: 0 AN: 58050

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	3.3
DANN	Benign	0.58
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.033
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.017
Sift	Benign	0.25	T
Sift4G	Benign	0.29	T
Polyphen		0.013	B
Vest4		0.29
MutPred		0.32		Loss of MoRF binding (P = 3e-04)
MVP		0.20
MPC		0.30
ClinPred		0.67	D
GERP RS		-3.4
gMVP		0.13
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs574552377; hg19: chr1-205492779;