1-1645238-CCTTTCTAA-C

Position:

• chr1-1645238-CCTTTCTAA-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033486.3(CDK11B):​c.511_518delTTAGAAAG​(p.Leu171fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000675 in 148,138 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: 𝑓 0.0000068 (0 hom., cov: 22)
• Consequence: CDK11B NM_033486.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.69

Genes affected

CDK11B (HGNC:1729): (cyclin dependent kinase 11B) 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, Apr 2014]

CDK11B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK11B	NM_033486.3	c.511_518delTTAGAAAG	p.Leu171fs	frameshift_variant	6/20	ENST00000341832.11	NP_277021.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK11B	ENST00000341832.11	c.511_518delTTAGAAAG	p.Leu171fs	frameshift_variant	6/20	1	NM_033486.3	ENSP00000463048.2

Frequencies

GnomAD3 genomes AF: 0.00000675 AC: 1 AN: 148138 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00000675 AC: 1 AN: 148138 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 72284

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Brachymorphism-onychodysplasia-dysphalangism syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

curation

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

Nov 25, 2024

The heterozygous p.Leu171GlufsTer118 variant in CDK11B was identified by our study, in the compound heterozygous state, in 2 siblings with Brachymorphism-onychodysplasia-dysphalangism syndrome. While this gene is still lacking sufficient evidence to establish a gene-disease relationship, we believe this is a possible novel gene candidate for Brachymorphism-onychodysplasia-dysphalangism syndrome. Given the limited information about this gene-disease relationship, the significance of the p.Leu171GlufsTer118 variant is uncertain. If you have any additional information about functional evidence or other individuals with this phenotype that also have variants in CDK11B we encourage you to reach out to us. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1557688217; hg19: chr1-1580599;