Variant 1-1703894-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_024011.4(CDK11A):c.1841G>A(p.Gly614Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,609,618 control chromosomes in the GnomAD database, including 4 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000025 ( 4 hom. )

Consequence

CDK11A
NM_024011.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17

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:

CDK11A (HGNC:):

CDK11A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK11A	NM_024011.4 linkuse as main transcript	c.1841G>A	p.Gly614Glu	missense_variant	17/20	ENST00000404249.8	NP_076916.2	Q9UQ88-2Q4VBY6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK11A	ENST00000404249.8 linkuse as main transcript	c.1841G>A	p.Gly614Glu	missense_variant	17/20	1	NM_024011.4	ENSP00000384442.3		Q9UQ88-2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000413

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000402

AC:

AN:

248734

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

134932

show subpopulations

Gnomad AFR exome

AF:

0.000647

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000254

AC:

AN:

1458408

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

725504

show subpopulations

Gnomad4 AFR exome

AF:

0.000957

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:

9.02e-7

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.000112

AC:

AN:

151210

Hom.:

Cov.:

AF XY:

0.0000813

AC XY:

AN XY:

73808

show subpopulations

Gnomad4 AFR

AF:

0.000413

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000967

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.000249

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000580

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

Sep 30, 2024

The c.1841G>A (p.G614E) alteration is located in exon 17 (coding exon 16) of the CDK11A gene. This alteration results from a G to A substitution at nucleotide position 1841, causing the glycine (G) at amino acid position 614 to be replaced by a glutamic acid (E). 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

Pathogenic

0.98

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.095

.;.;.;.;.;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.95

.;D;D;D;D;D

M_CAP

Benign

0.066

MetaRNN

Uncertain

0.73

D;D;D;D;D;D

MetaSVM

Uncertain

-0.044

MutationAssessor

Uncertain

2.2

.;.;.;.;.;M

PROVEAN

Uncertain

-3.0

D;D;D;D;D;D

REVEL

Uncertain

0.52

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;D;D;D

Polyphen

1.0

.;.;D;.;D;.

Vest4

0.82

MVP

0.66

MPC

0.25

ClinPred

0.39

GERP RS

2.3

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.76

gMVP

0.98

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