1-1704596-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024011.4(CDK11A):c.1518C>A(p.His506Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CDK11A NM_024011.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.348

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]

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=0.36088997).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK11A	NM_024011.4	c.1518C>A	p.His506Gln	missense_variant	14/20	ENST00000404249.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK11A	ENST00000404249.8	c.1518C>A	p.His506Gln	missense_variant	14/20	1	NM_024011.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2024

The c.1518C>A (p.H506Q) alteration is located in exon 14 (coding exon 13) of the CDK11A gene. This alteration results from a C to A substitution at nucleotide position 1518, causing the histidine (H) at amino acid position 506 to be replaced by a glutamine (Q). 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	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	12
Dann	Benign	0.93
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.28	N
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.36	T;T;T;T;T;T
MetaSVM	Benign	-0.70	T
MutationTaster	Benign	1.0	D;D;D;D;D;D
PROVEAN	Pathogenic	-7.4	D;D;D;D;D;D
REVEL	Uncertain	0.33
Sift	Benign	0.097	T;T;T;T;T;T
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		0.98	.;.;D;.;D;.
Vest4		0.41
MutPred		0.58		.;.;Loss of catalytic residue at D507 (P = 0.057);.;.;.;
MVP		0.38
MPC		0.19
ClinPred		0.68	D
GERP RS		-4.3
Varity_R		0.51
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-1636035;