12-96280831-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002595.5(CDK17):​c.1511G>A​(p.Arg504Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,613,780 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

CDK17
NM_002595.5 missense

Scores

6
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.48
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDK17NM_002595.5 linkc.1511G>A p.Arg504Gln missense_variant Exon 16 of 17 ENST00000261211.8 NP_002586.2 Q00537-1A0A024RBH0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDK17ENST00000261211.8 linkc.1511G>A p.Arg504Gln missense_variant Exon 16 of 17 1 NM_002595.5 ENSP00000261211.3 Q00537-1
CDK17ENST00000543119.6 linkc.1511G>A p.Arg504Gln missense_variant Exon 16 of 16 2 ENSP00000444459.2 Q00537-2
CDK17ENST00000542666.5 linkc.1352G>A p.Arg451Gln missense_variant Exon 15 of 15 2 ENSP00000442926.1 F5H6Z0

Frequencies

GnomAD3 genomes
AF:
0.000132
AC:
20
AN:
152090
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000120
AC:
30
AN:
250908
Hom.:
0
AF XY:
0.000118
AC XY:
16
AN XY:
135654
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000212
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000220
AC:
321
AN:
1461690
Hom.:
0
Cov.:
31
AF XY:
0.000205
AC XY:
149
AN XY:
727150
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000265
Gnomad4 OTH exome
AF:
0.000348
GnomAD4 genome
AF:
0.000132
AC:
20
AN:
152090
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74284
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000216
Hom.:
0
Bravo
AF:
0.000125
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000218
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1511G>A (p.R504Q) alteration is located in exon 16 (coding exon 15) of the CDK17 gene. This alteration results from a G to A substitution at nucleotide position 1511, causing the arginine (R) at amino acid position 504 to be replaced by a glutamine (Q). 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
Uncertain
0.52
BayesDel_addAF
Uncertain
0.061
T
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.11
T;.;T
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D;D;D
M_CAP
Benign
0.069
D
MetaRNN
Uncertain
0.59
D;D;D
MetaSVM
Uncertain
-0.22
T
MutationAssessor
Uncertain
2.9
M;M;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-2.3
N;N;N
REVEL
Uncertain
0.41
Sift
Benign
0.097
T;T;T
Sift4G
Benign
0.061
T;T;T
Polyphen
1.0
D;.;.
Vest4
0.87
MVP
0.74
MPC
1.3
ClinPred
0.69
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.28
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150884719; hg19: chr12-96674609; COSMIC: COSV54126529; COSMIC: COSV54126529; API