1-1703855-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_024011.4(CDK11A):āc.1880C>Gā(p.Ser627Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000373 in 1,609,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 31)
Exomes š: 0.0000034 ( 0 hom. )
Consequence
CDK11A
NM_024011.4 missense
NM_024011.4 missense
Scores
7
4
7
Clinical Significance
Conservation
PhyloP100: 7.00
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.852
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CDK11A | NM_024011.4 | c.1880C>G | p.Ser627Trp | missense_variant | 17/20 | ENST00000404249.8 | NP_076916.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CDK11A | ENST00000404249.8 | c.1880C>G | p.Ser627Trp | missense_variant | 17/20 | 1 | NM_024011.4 | ENSP00000384442.3 |
Frequencies
GnomAD3 genomes AF: 0.00000661 AC: 1AN: 151294Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248674Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134906
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GnomAD4 exome AF: 0.00000343 AC: 5AN: 1458368Hom.: 0 Cov.: 36 AF XY: 0.00000276 AC XY: 2AN XY: 725480
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GnomAD4 genome AF: 0.00000661 AC: 1AN: 151294Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 73848
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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 | Dec 03, 2024 | The c.1880C>G (p.S627W) alteration is located in exon 17 (coding exon 16) of the CDK11A gene. This alteration results from a C to G substitution at nucleotide position 1880, causing the serine (S) at amino acid position 627 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;.;.;.;.;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
.;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
.;.;.;.;.;M
PROVEAN
Pathogenic
D;D;D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D
Polyphen
1.0
.;.;D;.;D;.
Vest4
MutPred
0.63
.;.;Loss of disorder (P = 0.0112);.;.;.;
MVP
MPC
0.26
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at