Variant chr1-1703522-G-A 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.2014C>T(p.Arg672Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000552 in 1,557,456 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R672H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000052 ( 1 hom., cov: 17)

Exomes 𝑓: 0.000056 ( 2 hom. )

Consequence

CDK11A
NM_024011.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK11A	NM_024011.4 linkuse as main transcript	c.2014C>T	p.Arg672Cys	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.2014C>T	p.Arg672Cys	missense_variant	18/20	1	NM_024011.4	P1	Q9UQ88-2

Frequencies

GnomAD3 genomes

AF:

0.0000520

AC:

AN:

134640

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000361

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000139

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:

0.0000450

Gnomad OTH

AF:

0.000529

GnomAD3 exomes

AF:

0.0000786

AC:

AN:

203444

Hom.:

AF XY:

0.0000453

AC XY:

AN XY:

110468

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000134

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000399

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000866

Gnomad OTH exome

AF:

0.000380

GnomAD4 exome

AF:

0.0000555

AC:

AN:

1422816

Hom.:

Cov.:

AF XY:

0.0000567

AC XY:

AN XY:

705778

show subpopulations

Gnomad4 AFR exome

AF:

0.0000353

Gnomad4 AMR exome

AF:

0.0000993

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000620

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000530

Gnomad4 OTH exome

AF:

0.0000681

GnomAD4 genome

AF:

0.0000520

AC:

AN:

134640

Hom.:

Cov.:

AF XY:

0.0000612

AC XY:

AN XY:

65336

show subpopulations

Gnomad4 AFR

AF:

0.0000361

Gnomad4 AMR

AF:

0.000139

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000450

Gnomad4 OTH

AF:

0.000529

Alfa

AF:

0.000215

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000521

AC:

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

Nov 29, 2023

The c.2014C>T (p.R672C) alteration is located in exon 18 (coding exon 17) of the CDK11A gene. This alteration results from a C to T substitution at nucleotide position 2014, causing the arginine (R) at amino acid position 672 to be replaced by a cysteine (C). 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

Benign

0.21

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

.;.;.;.;.;T

Eigen

Benign

0.048

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.54

LIST_S2

Pathogenic

1.0

.;D;D;D;D;D

M_CAP

Benign

0.071

MetaRNN

Uncertain

0.61

D;D;D;D;D;D

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.8

.;.;.;.;.;L

MutationTaster

Benign

1.0

D;D;D;D;D;D

PROVEAN

Pathogenic

-5.5

D;D;D;D;D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0060

D;D;D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D;D

Polyphen

1.0

.;.;D;.;D;.

Vest4

0.71

MutPred

0.58

.;.;Gain of methylation at K671 (P = 0.0137);.;.;.;

MVP

0.32

MPC

0.26

ClinPred

0.39

GERP RS

-0.16

Varity_R

0.43

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