1-1704138-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_024011.4(CDK11A):c.1695T>C(p.Asp565=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 150,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000047 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00016 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDK11A NM_024011.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.969

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 1-1704138-A-G is Benign according to our data. Variant chr1-1704138-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2638056.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-1704138-A-G is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.969 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK11A	NM_024011.4	c.1695T>C	p.Asp565=	synonymous_variant	16/20	ENST00000404249.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK11A	ENST00000404249.8	c.1695T>C	p.Asp565=	synonymous_variant	16/20	1	NM_024011.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000466 AC: 7 AN: 150310 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000489

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.0000953

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000297

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000524 AC: 128 AN: 244330 Hom.: 1 AF XY: 0.000475 AC XY: 63 AN XY: 132600

Gnomad AFR exome AF: 0.000262

Gnomad AMR exome AF: 0.000410

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000558

Gnomad SAS exome AF: 0.000597

Gnomad FIN exome AF: 0.0000471

Gnomad NFE exome AF: 0.000791

Gnomad OTH exome AF: 0.000507

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000162 AC: 235 AN: 1451348 Hom.: 4 Cov.: 38 AF XY: 0.000205 AC XY: 148 AN XY: 721706

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000248

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000806

Gnomad4 FIN exome AF: 0.0000753

Gnomad4 NFE exome AF: 0.000114

Gnomad4 OTH exome AF: 0.000284

GnomAD4 genome AF: 0.0000465 AC: 7 AN: 150424 Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1 AN XY: 73476

Gnomad4 AFR AF: 0.0000488

Gnomad4 AMR AF: 0.0000662

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000211

Gnomad4 FIN AF: 0.0000953

Gnomad4 NFE AF: 0.0000297

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00149 Hom.: 0

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

Nov 01, 2022

CDK11A: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	7.0
Dann	Benign	0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1136996; hg19: chr1-1635577; COSMIC: COSV52307171; COSMIC: COSV52307171;