1-1707458-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024011.4(CDK11A):ā€‹c.1196T>Cā€‹(p.Leu399Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00283 in 148,598 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0028 ( 2 hom., cov: 28)
Exomes š‘“: 0.00019 ( 22 hom. )
Failed GnomAD Quality Control

Consequence

CDK11A
NM_024011.4 missense

Scores

17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.41
Variant links:
Genes affected
CDK11A (HGNC:1730): (cyclin dependent kinase 11A) This gene encodes a member of the serine/threonine protein kinase family. Members of this kinase family are known to be essential for eukaryotic cell cycle control. Due to a segmental duplication, this gene shares very high sequence identity with a neighboring gene. These two genes are frequently deleted or altered in neuroblastoma. The protein kinase encoded by this gene can be cleaved by caspases and may play a role in cell apoptosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.005014986).
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CDK11ANM_024011.4 linkuse as main transcriptc.1196T>C p.Leu399Ser missense_variant 11/20 ENST00000404249.8 NP_076916.2 Q9UQ88-2Q4VBY6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CDK11AENST00000404249.8 linkuse as main transcriptc.1196T>C p.Leu399Ser missense_variant 11/201 NM_024011.4 ENSP00000384442.3 Q9UQ88-2

Frequencies

GnomAD3 genomes
AF:
0.00283
AC:
420
AN:
148488
Hom.:
2
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.00979
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000869
Gnomad ASJ
AF:
0.000583
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000214
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000193
Gnomad OTH
AF:
0.00299
GnomAD3 exomes
AF:
0.00348
AC:
849
AN:
244268
Hom.:
37
AF XY:
0.00328
AC XY:
435
AN XY:
132584
show subpopulations
Gnomad AFR exome
AF:
0.0240
Gnomad AMR exome
AF:
0.00160
Gnomad ASJ exome
AF:
0.000801
Gnomad EAS exome
AF:
0.00426
Gnomad SAS exome
AF:
0.00571
Gnomad FIN exome
AF:
0.000233
Gnomad NFE exome
AF:
0.00152
Gnomad OTH exome
AF:
0.00320
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000192
AC:
279
AN:
1455460
Hom.:
22
Cov.:
31
AF XY:
0.000171
AC XY:
124
AN XY:
723980
show subpopulations
Gnomad4 AFR exome
AF:
0.00601
Gnomad4 AMR exome
AF:
0.000382
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.000187
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000244
Gnomad4 OTH exome
AF:
0.000267
GnomAD4 genome
AF:
0.00283
AC:
421
AN:
148598
Hom.:
2
Cov.:
28
AF XY:
0.00266
AC XY:
193
AN XY:
72622
show subpopulations
Gnomad4 AFR
AF:
0.00978
Gnomad4 AMR
AF:
0.000868
Gnomad4 ASJ
AF:
0.000583
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000214
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000193
Gnomad4 OTH
AF:
0.00296
Alfa
AF:
0.00165
Hom.:
4
ExAC
AF:
0.00913
AC:
1102
EpiCase
AF:
0.00378
EpiControl
AF:
0.00305

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.047
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
17
DANN
Benign
0.18
DEOGEN2
Benign
0.018
.;.;.;.;.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.91
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.26
.;T;T;T;T;T
MetaRNN
Benign
0.0050
T;T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
-1.0
.;.;.;.;.;N
PROVEAN
Benign
2.4
N;N;N;N;N;N
REVEL
Benign
0.13
Sift
Benign
1.0
T;T;T;T;T;T
Sift4G
Benign
0.89
T;T;T;T;T;T
Polyphen
0.0
.;.;B;.;B;.
Vest4
0.33
MVP
0.12
MPC
0.27
ClinPred
0.0020
T
GERP RS
2.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.029
gMVP
0.22

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: rs1059828; hg19: chr1-1638897; COSMIC: COSV62265934; COSMIC: COSV62265934; API