chr12-96280837-C-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_002595.5(CDK17):​c.1505G>C​(p.Gly502Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,613,830 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: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

CDK17
NM_002595.5 missense

Scores

4
8
7

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 -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.3698104).
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDK17NM_002595.5 linkc.1505G>C p.Gly502Ala 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.1505G>C p.Gly502Ala missense_variant Exon 16 of 17 1 NM_002595.5 ENSP00000261211.3 Q00537-1
CDK17ENST00000543119.6 linkc.1505G>C p.Gly502Ala missense_variant Exon 16 of 16 2 ENSP00000444459.2 Q00537-2
CDK17ENST00000542666.5 linkc.1346G>C p.Gly449Ala missense_variant Exon 15 of 15 2 ENSP00000442926.1 F5H6Z0

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152120
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000441
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
250950
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135678
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000506
AC:
74
AN:
1461710
Hom.:
0
Cov.:
31
AF XY:
0.0000440
AC XY:
32
AN XY:
727158
show subpopulations
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:
0.0000666
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152120
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000900
Hom.:
0
Bravo
AF:
0.0000189
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 05, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1505G>C (p.G502A) alteration is located in exon 16 (coding exon 15) of the CDK17 gene. This alteration results from a G to C substitution at nucleotide position 1505, causing the glycine (G) at amino acid position 502 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
Uncertain
0.55
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.27
T;.;T
Eigen
Uncertain
0.66
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.37
T;T;T
MetaSVM
Benign
-0.35
T
MutationAssessor
Uncertain
2.9
M;M;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-3.0
D;D;D
REVEL
Uncertain
0.43
Sift
Benign
0.082
T;T;T
Sift4G
Benign
0.28
T;T;D
Polyphen
0.85
P;.;.
Vest4
0.72
MVP
0.71
MPC
1.7
ClinPred
0.52
D
GERP RS
5.9
Varity_R
0.31
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

LitVar

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

Other links and lift over

dbSNP: rs200258723; hg19: chr12-96674615; API