12-96311144-T-G

Variant names:

• chr12-96311144-T-G
• NM_002595.5:c.451A>C

Variant summary

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

The NM_002595.5(CDK17):​c.451A>C​(p.Ile151Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,438,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CDK17 NM_002595.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67

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

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=0.31482834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK17	NM_002595.5	c.451A>C	p.Ile151Leu	missense_variant	Exon 5 of 17	ENST00000261211.8	NP_002586.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK17	ENST00000261211.8	c.451A>C	p.Ile151Leu	missense_variant	Exon 5 of 17	1	NM_002595.5	ENSP00000261211.3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1438230 Hom.: 0 Cov.: 30 AF XY: 0.00000280 AC XY: 2 AN XY: 715420

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: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.451A>C (p.I151L) alteration is located in exon 5 (coding exon 4) of the CDK17 gene. This alteration results from a A to C substitution at nucleotide position 451, causing the isoleucine (I) at amino acid position 151 to be replaced by a leucine (L). 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
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.073	T;.;T;T;T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.31	T;T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.7	L;L;.;.;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.76	N;N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.18	T;T;T;T;T
Sift4G	Benign	0.40	T;T;T;T;T
Polyphen		0.054	B;.;.;.;.
Vest4		0.51
MutPred		0.16		Gain of catalytic residue at I151 (P = 0.1842);Gain of catalytic residue at I151 (P = 0.1842);.;Gain of catalytic residue at I151 (P = 0.1842);Gain of catalytic residue at I151 (P = 0.1842);
MVP		0.79
MPC		0.65
ClinPred		0.81	D
GERP RS		5.6
Varity_R		0.27
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-96704922;