rs718652

Variant names:

• chr13-26406453-A-G
• rs718652
• ENST00000700505.1:n.1074+2298A>G

Variant summary

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

The ENST00000700505.1(CDK8):​n.1074+2298A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,848 control chromosomes in the GnomAD database, including 14,701 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 0.41 (14701 hom., cov: 31)
• Consequence: CDK8 ENST00000700505.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.868
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK8	ENST00000700505.1	n.1074+2298A>G		intron_variant	Intron 10 of 10

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62706 AN: 151730 Hom.: 14716 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.413 AC: 62664 AN: 151848 Hom.: 14701 Cov.: 31 AF XY: 0.415 AC XY: 30802 AN XY: 74214

African (AFR) AF: 0.174 AC: 7206 AN: 41398

American (AMR) AF: 0.444 AC: 6776 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1884 AN: 3466

East Asian (EAS) AF: 0.393 AC: 2016 AN: 5126

South Asian (SAS) AF: 0.450 AC: 2156 AN: 4796

European-Finnish (FIN) AF: 0.524 AC: 5523 AN: 10548

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35526 AN: 67944

Other (OTH) AF: 0.436 AC: 919 AN: 2108

Alfa AF: 0.457 Hom.: 2348

Bravo AF: 0.391

Asia WGS AF: 0.400 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.013
DANN	Benign	0.65
PhyloP100		-0.87

Splicing

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

Other links and lift over

dbSNP: rs718652; hg19: chr13-26980590;