13-26266711-C-T

Variant names:

• chr13-26266711-C-T
• rs9319288
• NM_001260.3:c.128+11942C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001260.3(CDK8):​c.128+11942C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,168 control chromosomes in the GnomAD database, including 2,642 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (2642 hom., cov: 32)
• Consequence: CDK8 NM_001260.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 1 publications found

Genes affected

CDK8 (HGNC:1779): (cyclin dependent kinase 8) This gene encodes a member of the cyclin-dependent protein kinase (CDK) family. CDK family members are known to be important regulators of cell cycle progression. This kinase and its regulatory subunit, cyclin C, are components of the Mediator transcriptional regulatory complex, involved in both transcriptional activation and repression by phosphorylation of the carboxy-terminal domain of the largest subunit of RNA polymerase II. This kinase regulates transcription by targeting the cyclin-dependent kinase 7 subunits of the general transcription initiation factor IIH, thus providing a link between the Mediator complex and the basal transcription machinery. Multiple pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

CDK8 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with hypotonia and behavioral abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001260.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK8	NM_001260.3	MANE Select	c.128+11942C>T		intron	N/A	NP_001251.1
	CDK8	NM_001318368.2		c.128+11942C>T		intron	N/A	NP_001305297.1
	CDK8	NM_001346501.2		c.-334+11942C>T		intron	N/A	NP_001333430.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK8	ENST00000381527.8	TSL:1 MANE Select	c.128+11942C>T		intron	N/A	ENSP00000370938.3
	CDK8	ENST00000536792.5	TSL:1	n.128+11942C>T		intron	N/A	ENSP00000437696.1
	CDK8	ENST00000700501.1		n.128+11942C>T		intron	N/A	ENSP00000515024.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16439 AN: 152050 Hom.: 2634 Cov.: 32

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0807

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

GnomAD4 genome AF: 0.108 AC: 16481 AN: 152168 Hom.: 2642 Cov.: 32 AF XY: 0.104 AC XY: 7714 AN XY: 74414

African (AFR) AF: 0.353 AC: 14633 AN: 41452

American (AMR) AF: 0.0434 AC: 663 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0184 AC: 89 AN: 4826

European-Finnish (FIN) AF: 0.00358 AC: 38 AN: 10608

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0120 AC: 819 AN: 68020

Other (OTH) AF: 0.0803 AC: 170 AN: 2116

Alfa AF: 0.0795 Hom.: 237

Bravo AF: 0.124

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.55
PhyloP100		-0.055
Mutation Taster		=100/0	polymorphism (auto)

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: rs9319288; hg19: chr13-26840848;