NM_024011.4:c.277C>G

Variant names:

• chr1-1719406-G-C
• rs1059831
• NM_024011.4:c.277C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.25
• Publications: 30 publications found

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]

ENSG00000268575 (HGNC:):

ACMG classification

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024011.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK11A	NM_024011.4	MANE Select	c.277C>G	p.Arg93Gly	missense	Exon 4 of 20	NP_076916.2	Q9UQ88-2
	CDK11A	NM_001313896.2		c.277C>G	p.Arg93Gly	missense	Exon 4 of 20	NP_001300825.1	Q9UQ88-1
	CDK11A	NM_001313982.2		c.277C>G	p.Arg93Gly	missense	Exon 4 of 20	NP_001300911.1	Q5QPR3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK11A	ENST00000404249.8	TSL:1 MANE Select	c.277C>G	p.Arg93Gly	missense	Exon 4 of 20	ENSP00000384442.3	Q9UQ88-2
	CDK11A	ENST00000378633.5	TSL:1	c.277C>G	p.Arg93Gly	missense	Exon 4 of 20	ENSP00000367900.1	Q9UQ88-1
	CDK11A	ENST00000357760.6	TSL:1	c.277C>G	p.Arg93Gly	missense	Exon 4 of 20	ENSP00000350403.2	Q5QPR3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000204 AC: 28 AN: 1373506 Hom.: 0 Cov.: 31 AF XY: 0.0000205 AC XY: 14 AN XY: 682144

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

African (AFR) AF: 0.00 AC: 0 AN: 29890

American (AMR) AF: 0.00 AC: 0 AN: 28252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23482

East Asian (EAS) AF: 0.00 AC: 0 AN: 35558

South Asian (SAS) AF: 0.00 AC: 0 AN: 73586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5476

European-Non Finnish (NFE) AF: 0.0000253 AC: 27 AN: 1068464

Other (OTH) AF: 0.0000177 AC: 1 AN: 56618

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 1068

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.3
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.26
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.029	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.14		Loss of MoRF binding (P = 0.0213)
MVP		0.43
MPC		0.85
ClinPred		0.84	D
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

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

Other links and lift over

dbSNP: rs1059831; hg19: chr1-1650845;