Genetic Variant CDK11A:p.Arg93Gly (chr1-1719406-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_024011.4(CDK11A):c.277C>G(p.Arg93Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000204 in 1,373,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

CDK11A
NM_024011.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.25

Publications

30 publications found

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:

ENSG00000268575 (HGNC:):

ENSG00000268575 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4005287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK11A	NM_024011.4 link	c.277C>G	p.Arg93Gly	missense_variant	Exon 4 of 20	ENST00000404249.8	NP_076916.2	Q9UQ88-2Q4VBY6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK11A	ENST00000404249.8 link	c.277C>G	p.Arg93Gly	missense_variant	Exon 4 of 20	1	NM_024011.4	ENSP00000384442.3		Q9UQ88-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000204

AC:

AN:

1373506

Hom.:

Cov.:

AF XY:

0.0000205

AC XY:

AN XY:

682144

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

29890

American (AMR)

AF:

0.00

AC:

AN:

28252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23482

East Asian (EAS)

AF:

0.00

AC:

AN:

35558

South Asian (SAS)

AF:

0.00

AC:

AN:

73586

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52180

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5476

European-Non Finnish (NFE)

AF:

0.0000253

AC:

AN:

1068464

Other (OTH)

AF:

0.0000177

AC:

AN:

56618

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.355

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

1068

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

.;.;.;.;.;T;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

.;D;D;D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.40

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

.;.;M;.;M;M;.

PhyloP100

6.3

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.3

N;N;N;N;N;N;D

REVEL

Benign

0.26

Sift

Uncertain

0.0030

D;D;D;D;D;D;T

Sift4G

Uncertain

0.029

D;D;T;T;D;D;.

Polyphen

1.0

D;D;D;D;P;D;.

Vest4

0.53

MutPred

0.14

.;.;Loss of MoRF binding (P = 0.0213);Loss of MoRF binding (P = 0.0213);Loss of MoRF binding (P = 0.0213);Loss of MoRF binding (P = 0.0213);Loss of MoRF binding (P = 0.0213);

MVP

0.43

MPC

0.85

ClinPred

0.84

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.055

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over