Variant 1-1703489-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024011.4(CDK11A):c.2047G>A(p.Asp683Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000272 in 1,526,524 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. D683D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00058 ( 2 hom., cov: 17)

Exomes 𝑓: 0.00024 ( 17 hom. )

Consequence

CDK11A
NM_024011.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.06

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]

CDK11A links:

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=0.02270171).

BP6

Variant 1-1703489-C-T is Benign according to our data. Variant chr1-1703489-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638053.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK11A	NM_024011.4 linkuse as main transcript	c.2047G>A	p.Asp683Asn	missense_variant	18/20	ENST00000404249.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK11A	ENST00000404249.8 linkuse as main transcript	c.2047G>A	p.Asp683Asn	missense_variant	18/20	1	NM_024011.4	P1	Q9UQ88-2

Frequencies

GnomAD3 genomes

AF:

0.000578

AC:

AN:

128030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000421

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00237

Gnomad ASJ

AF:

0.00833

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000251

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000168

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000531

AC:

AN:

162008

Hom.:

AF XY:

0.000507

AC XY:

AN XY:

86836

show subpopulations

Gnomad AFR exome

AF:

0.000274

Gnomad AMR exome

AF:

0.000635

Gnomad ASJ exome

AF:

0.00668

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000890

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000121

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000244

AC:

341

AN:

1398422

Hom.:

Cov.:

AF XY:

0.000226

AC XY:

156

AN XY:

691198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000661

Gnomad4 ASJ exome

AF:

0.00627

Gnomad4 EAS exome

AF:

0.0000276

Gnomad4 SAS exome

AF:

0.000153

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000101

Gnomad4 OTH exome

AF:

0.000624

GnomAD4 genome

AF:

0.000578

AC:

AN:

128102

Hom.:

Cov.:

AF XY:

0.000791

AC XY:

AN XY:

61954

show subpopulations

Gnomad4 AFR

AF:

0.0000419

Gnomad4 AMR

AF:

0.00237

Gnomad4 ASJ

AF:

0.00833

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000251

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000168

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000881

Hom.:

Bravo

AF:

0.000529

ESP6500AA

AF:

0.000336

AC:

ESP6500EA

AF:

0.000505

AC:

ExAC

AF:

0.000226

AC:

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 submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

CDK11A: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

.;.;.;.;.;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.28

FATHMM_MKL

Uncertain

0.86

LIST_S2

Pathogenic

0.99

.;D;D;D;D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.023

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

.;.;.;.;.;L

MutationTaster

Benign

1.0

D;D;D;D;D;D

PROVEAN

Benign

-1.3

N;N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.066

T;T;T;T;T;T

Sift4G

Benign

0.18

T;T;T;T;T;T

Polyphen

0.37

.;.;B;.;B;.

Vest4

0.57

MVP

0.32

MPC

0.19

ClinPred

0.035

GERP RS

1.6

Varity_R

0.10

gMVP

0.81

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over