NM_052988.5:c.139delG

Variant names:

• chr16-89689302-AG-A
• rs1555516716
• NM_052988.5:c.139delG

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_052988.5(CDK10):​c.139delG​(p.Glu47ArgfsTer21) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK10 NM_052988.5 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:3
• Conservation: PhyloP100: 8.90
• Publications: 0 publications found

Genes affected

CDK10 (HGNC:1770): (cyclin dependent kinase 10) The protein encoded by this gene belongs to the CDK subfamily of the Ser/Thr protein kinase family. The CDK subfamily members are highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, and are known to be essential for cell cycle progression. This kinase has been shown to play a role in cellular proliferation and its function is limited to cell cycle G2-M phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

CDK10 Gene-Disease associations (from GenCC):

• Al Kaissi syndrome

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-89689302-AG-A is Pathogenic according to our data. Variant chr16-89689302-AG-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 440756.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052988.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK10	NM_052988.5	MANE Select	c.139delG	p.Glu47ArgfsTer21	frameshift	Exon 2 of 13	NP_443714.3
	CDK10	NM_001160367.2		c.-75delG		5_prime_UTR	Exon 2 of 13	NP_001153839.1	Q15131-2
	CDK10	NM_001098533.3		c.-75delG		5_prime_UTR	Exon 2 of 13	NP_001092003.2	Q15131-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK10	ENST00000353379.12	TSL:1 MANE Select	c.139delG	p.Glu47ArgfsTer21	frameshift	Exon 2 of 13	ENSP00000338673.7	Q15131-1
	CDK10	ENST00000505473.5	TSL:1	c.-75delG		5_prime_UTR	Exon 2 of 13	ENSP00000424415.1	Q15131-4
	CDK10	ENST00000851882.1		c.139delG	p.Glu47ArgfsTer21	frameshift	Exon 2 of 13	ENSP00000521941.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
3	-	-	Al Kaissi syndrome (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.9
Mutation Taster		=14/186	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs1555516716; hg19: chr16-89755710;