1-1704076-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_024011.4(CDK11A):​c.1757A>T​(p.Gln586Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,595,632 control chromosomes in the GnomAD database, including 168 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 11 hom., cov: 31)
Exomes 𝑓: 0.0024 ( 157 hom. )

Consequence

CDK11A
NM_024011.4 missense

Scores

18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.40
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.010631949).
BP6
Variant 1-1704076-T-A is Benign according to our data. Variant chr1-1704076-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638054.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDK11ANM_024011.4 linkuse as main transcriptc.1757A>T p.Gln586Leu missense_variant 16/20 ENST00000404249.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDK11AENST00000404249.8 linkuse as main transcriptc.1757A>T p.Gln586Leu missense_variant 16/201 NM_024011.4 P1Q9UQ88-2

Frequencies

GnomAD3 genomes
AF:
0.00206
AC:
310
AN:
150588
Hom.:
11
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000586
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000663
Gnomad ASJ
AF:
0.00116
Gnomad EAS
AF:
0.000195
Gnomad SAS
AF:
0.000631
Gnomad FIN
AF:
0.00836
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00264
Gnomad OTH
AF:
0.000982
GnomAD3 exomes
AF:
0.00238
AC:
569
AN:
238886
Hom.:
11
AF XY:
0.00247
AC XY:
319
AN XY:
129304
show subpopulations
Gnomad AFR exome
AF:
0.000591
Gnomad AMR exome
AF:
0.000266
Gnomad ASJ exome
AF:
0.00122
Gnomad EAS exome
AF:
0.0000562
Gnomad SAS exome
AF:
0.000838
Gnomad FIN exome
AF:
0.00749
Gnomad NFE exome
AF:
0.00320
Gnomad OTH exome
AF:
0.00242
GnomAD4 exome
AF:
0.00243
AC:
3508
AN:
1444932
Hom.:
157
Cov.:
37
AF XY:
0.00239
AC XY:
1714
AN XY:
717236
show subpopulations
Gnomad4 AFR exome
AF:
0.000271
Gnomad4 AMR exome
AF:
0.000341
Gnomad4 ASJ exome
AF:
0.00203
Gnomad4 EAS exome
AF:
0.0000760
Gnomad4 SAS exome
AF:
0.000594
Gnomad4 FIN exome
AF:
0.00788
Gnomad4 NFE exome
AF:
0.00258
Gnomad4 OTH exome
AF:
0.00200
GnomAD4 genome
AF:
0.00206
AC:
310
AN:
150700
Hom.:
11
Cov.:
31
AF XY:
0.00232
AC XY:
171
AN XY:
73606
show subpopulations
Gnomad4 AFR
AF:
0.000585
Gnomad4 AMR
AF:
0.000662
Gnomad4 ASJ
AF:
0.00116
Gnomad4 EAS
AF:
0.000196
Gnomad4 SAS
AF:
0.000631
Gnomad4 FIN
AF:
0.00836
Gnomad4 NFE
AF:
0.00264
Gnomad4 OTH
AF:
0.000973
Alfa
AF:
0.00223
Hom.:
5
Bravo
AF:
0.00147
ESP6500AA
AF:
0.00146
AC:
6
ESP6500EA
AF:
0.00227
AC:
19
ExAC
AF:
0.00350
AC:
422

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2023CDK11A: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.034
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
12
DANN
Benign
0.59
DEOGEN2
Benign
0.014
.;.;.;.;.;T
Eigen
Benign
-2.2
Eigen_PC
Benign
-2.1
FATHMM_MKL
Benign
0.0067
N
LIST_S2
Benign
0.36
.;T;T;T;T;T
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.011
T;T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
-1.8
.;.;.;.;.;N
MutationTaster
Benign
1.0
N;N;N;N;N;N
PROVEAN
Benign
4.7
N;N;N;N;N;N
REVEL
Benign
0.17
Sift
Benign
1.0
T;T;T;T;T;T
Sift4G
Benign
1.0
T;T;T;T;T;T
Polyphen
0.0
.;.;B;.;B;.
Vest4
0.26
MVP
0.21
MPC
0.19
ClinPred
0.0054
T
GERP RS
-2.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.047
gMVP
0.78

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs56410233; hg19: chr1-1635515; COSMIC: COSV52307950; COSMIC: COSV52307950; API