1-1719406-G-C

Position:

• chr1-1719406-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R93W) has been classified as Likely benign.

• 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

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

Verdict is Uncertain_significance. Variant got 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/exons	MANE	Protein	UniProt
CDK11A	NM_024011.4	c.277C>G	p.Arg93Gly	missense_variant	4/20	ENST00000404249.8	NP_076916.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK11A	ENST00000404249.8	c.277C>G	p.Arg93Gly	missense_variant	4/20	1	NM_024011.4	ENSP00000384442.3

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

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000253

Gnomad4 OTH exome AF: 0.0000177

GnomAD4 genome Cov.: 31

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	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;D;D;D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.40	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	.;.;M;.;M;M;.
PrimateAI	Pathogenic	0.80	T
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	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.055

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

Other links and lift over

dbSNP: rs1059831; hg19: chr1-1650845;