2-201880063-C-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001366386.2(CDK15):āc.1094C>Gā(p.Ser365Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.000039 ( 0 hom. )
Consequence
CDK15
NM_001366386.2 missense
NM_001366386.2 missense
Scores
1
9
6
Clinical Significance
Conservation
PhyloP100: 2.01
Genes affected
CDK15 (HGNC:14434): (cyclin dependent kinase 15) Enables protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation and regulation of transcription involved in G1/S transition of mitotic cell cycle. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.745
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDK15 | NM_001366386.2 | c.1094C>G | p.Ser365Cys | missense_variant | 12/14 | ENST00000652192.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDK15 | ENST00000652192.3 | c.1094C>G | p.Ser365Cys | missense_variant | 12/14 | NM_001366386.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152134Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
3
AN:
152134
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251182Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135760
GnomAD3 exomes
AF:
AC:
7
AN:
251182
Hom.:
AF XY:
AC XY:
2
AN XY:
135760
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461848Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23AN XY: 727222
GnomAD4 exome
AF:
AC:
57
AN:
1461848
Hom.:
Cov.:
31
AF XY:
AC XY:
23
AN XY:
727222
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74316
GnomAD4 genome
AF:
AC:
3
AN:
152134
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74316
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
AF:
AC:
3
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 10, 2022 | The c.941C>G (p.S314C) alteration is located in exon 12 (coding exon 11) of the CDK15 gene. This alteration results from a C to G substitution at nucleotide position 941, causing the serine (S) at amino acid position 314 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;T
Vest4
MVP
MPC
0.36
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at