1-1703489-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_024011.4(CDK11A):c.2047G>A(p.Asp683Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000272 in 1,526,524 control chromosomes in the GnomAD database, including 19 homozygotes. 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. D683D) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00058 (2 hom., cov: 17)
  • Exomes 𝑓: 0.00024 (17 hom.)
• Consequence: CDK11A NM_024011.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.06

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02270171).
• BP6: Variant 1-1703489-C-T is Benign according to our data. Variant chr1-1703489-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638053.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK11A	NM_024011.4	c.2047G>A	p.Asp683Asn	missense_variant	18/20	ENST00000404249.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK11A	ENST00000404249.8	c.2047G>A	p.Asp683Asn	missense_variant	18/20	1	NM_024011.4	P1

Frequencies

GnomAD3 genomes AF: 0.000578 AC: 74 AN: 128030 Hom.: 2 Cov.: 17

Gnomad AFR AF: 0.0000421

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00237

Gnomad ASJ AF: 0.00833

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000251

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000168

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000531 AC: 86 AN: 162008 Hom.: 4 AF XY: 0.000507 AC XY: 44 AN XY: 86836

Gnomad AFR exome AF: 0.000274

Gnomad AMR exome AF: 0.000635

Gnomad ASJ exome AF: 0.00668

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000890

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000121

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.000244 AC: 341 AN: 1398422 Hom.: 17 Cov.: 30 AF XY: 0.000226 AC XY: 156 AN XY: 691198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000661

Gnomad4 ASJ exome AF: 0.00627

Gnomad4 EAS exome AF: 0.0000276

Gnomad4 SAS exome AF: 0.000153

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000101

Gnomad4 OTH exome AF: 0.000624

GnomAD4 genome AF: 0.000578 AC: 74 AN: 128102 Hom.: 2 Cov.: 17 AF XY: 0.000791 AC XY: 49 AN XY: 61954

Gnomad4 AFR AF: 0.0000419

Gnomad4 AMR AF: 0.00237

Gnomad4 ASJ AF: 0.00833

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000251

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000168

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000881 Hom.: 2

Bravo AF: 0.000529

ESP6500AA AF: 0.000336 AC: 1

ESP6500EA AF: 0.000505 AC: 4

ExAC AF: 0.000226 AC: 25

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

CDK11A: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.39
Cadd	Uncertain	24
Dann	Uncertain	0.99
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.023	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;D;D;D
PROVEAN	Benign	-1.3	N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.066	T;T;T;T;T;T
Sift4G	Benign	0.18	T;T;T;T;T;T
Polyphen		0.37	.;.;B;.;B;.
Vest4		0.57
MVP		0.32
MPC		0.19
ClinPred		0.035	T
GERP RS		1.6
Varity_R		0.10
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs368698821; hg19: chr1-1634928;