12-96286083-G-C

Variant names:

• chr12-96286083-G-C
• NM_002595.5:c.1282C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002595.5(CDK17):​c.1282C>G​(p.Pro428Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000285 in 1,405,824 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: CDK17 NM_002595.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.89

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK17	NM_002595.5	c.1282C>G	p.Pro428Ala	missense_variant	Exon 13 of 17	ENST00000261211.8	NP_002586.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK17	ENST00000261211.8	c.1282C>G	p.Pro428Ala	missense_variant	Exon 13 of 17	1	NM_002595.5	ENSP00000261211.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000285 AC: 4 AN: 1405824 Hom.: 0 Cov.: 27 AF XY: 0.00000429 AC XY: 3 AN XY: 699688

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: 0.00000370

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1282C>G (p.P428A) alteration is located in exon 13 (coding exon 12) of the CDK17 gene. This alteration results from a C to G substitution at nucleotide position 1282, causing the proline (P) at amino acid position 428 to be replaced by an alanine (A). 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	0.22
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Benign	0.20	T;.;T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.51	D;D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.7	M;M;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.1	D;D;D
REVEL	Uncertain	0.41
Sift	Benign	0.052	T;D;D
Sift4G	Benign	0.096	T;T;D
Polyphen		0.79	P;.;.
Vest4		0.54
MutPred		0.51		Loss of glycosylation at P428 (P = 0.0465);Loss of glycosylation at P428 (P = 0.0465);.;
MVP		0.40
MPC		0.83
ClinPred		0.80	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.63

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: chr12-96679861;