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GeneBe

1-1704133-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_024011.4(CDK11A):c.1700G>A(p.Gly567Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,454,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

CDK11A
NM_024011.4 missense

Scores

8
4
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.96
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.989

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDK11ANM_024011.4 linkuse as main transcriptc.1700G>A p.Gly567Glu missense_variant 16/20 ENST00000404249.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDK11AENST00000404249.8 linkuse as main transcriptc.1700G>A p.Gly567Glu missense_variant 16/201 NM_024011.4 P1Q9UQ88-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000408
AC:
10
AN:
244914
Hom.:
0
AF XY:
0.0000452
AC XY:
6
AN XY:
132888
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000333
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1454494
Hom.:
0
Cov.:
38
AF XY:
0.0000138
AC XY:
10
AN XY:
723188
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000152
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000181
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.0000580
AC:
7

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 submitterclinical testingAmbry GeneticsFeb 07, 2023The c.1700G>A (p.G567E) alteration is located in exon 16 (coding exon 15) of the CDK11A gene. This alteration results from a G to A substitution at nucleotide position 1700, causing the glycine (G) at amino acid position 567 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
0.99
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Pathogenic
0.41
Cadd
Uncertain
24
Dann
Benign
0.89
Eigen
Uncertain
0.51
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.96
D
M_CAP
Uncertain
0.15
D
MetaRNN
Pathogenic
0.99
D;D;D;D;D;D
MetaSVM
Pathogenic
0.95
D
MutationTaster
Benign
1.0
D;D;D;D;D;D
PROVEAN
Pathogenic
-7.2
D;D;D;D;D;D
REVEL
Pathogenic
0.72
Sift
Pathogenic
0.0
D;D;D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D;D;D
Polyphen
1.0
.;.;D;.;D;.
Vest4
0.95
MutPred
0.97
.;.;Loss of sheet (P = 0.1158);.;.;.;
MVP
0.82
MPC
0.25
ClinPred
0.92
D
GERP RS
2.6
Varity_R
0.84
gMVP
0.96

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs758938952; hg19: chr1-1635572; API