rs139401006

Variant names:

• chr12-96282544-C-G
• rs139401006
• NM_002595.5:c.1421G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-96282544-C-G
• chr12-96282544-C-T

Variant summary

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

The NM_002595.5(CDK17):​c.1421G>C​(p.Arg474Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R474Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK17 NM_002595.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.02
• Publications: 0 publications found

Genes affected

CDK17 (HGNC:8750): (cyclin dependent kinase 17) The protein encoded by this gene belongs to the cdc2/cdkx subfamily of the ser/thr family of protein kinases. It has similarity to a rat protein that is thought to play a role in terminally differentiated neurons. Alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002595.5. 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
	CDK17	NM_002595.5	MANE Select	c.1421G>C	p.Arg474Pro	missense	Exon 15 of 17	NP_002586.2
	CDK17	NM_001170464.4		c.1421G>C	p.Arg474Pro	missense	Exon 15 of 16	NP_001163935.1	Q00537-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK17	ENST00000261211.8	TSL:1 MANE Select	c.1421G>C	p.Arg474Pro	missense	Exon 15 of 17	ENSP00000261211.3	Q00537-1
	CDK17	ENST00000859519.1		c.1442G>C	p.Arg481Pro	missense	Exon 15 of 17	ENSP00000529578.1
	CDK17	ENST00000964179.1		c.1442G>C	p.Arg481Pro	missense	Exon 16 of 18	ENSP00000634238.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.0
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.20
Sift	Benign	0.091	T
Sift4G	Benign	0.14	T
Polyphen		0.32	B
Vest4		0.72
MutPred		0.46		Loss of MoRF binding (P = 0.0325)
MVP		0.36
MPC		1.1
ClinPred		0.89	D
GERP RS		6.2
Varity_R		0.87
gMVP		0.86
Mutation Taster		=29/71	disease causing

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: rs139401006; hg19: chr12-96676322;