rs2691180

Variant names:

• chr6-110630803-A-C
• rs2691180
• NM_015076.5:c.646+1227T>G

Variant summary

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

The NM_015076.5(CDK19):​c.646+1227T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,150 control chromosomes in the GnomAD database, including 3,908 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 0.22 (3908 hom., cov: 33)
• Consequence: CDK19 NM_015076.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 1 publications found

Genes affected

CDK19 (HGNC:19338): (cyclin dependent kinase 19) This gene encodes a protein that is one of the components of the Mediator co-activator complex. The Mediator complex is a multi-protein complex required for transcriptional activation by DNA binding transcription factors of genes transcribed by RNA polymerase II. The protein encoded by this gene is similar to cyclin-dependent kinase 8 which can also be a component of the Mediator complex. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

CDK19 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 87

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK19	NM_015076.5	c.646+1227T>G		intron_variant	Intron 6 of 12	ENST00000368911.8	NP_055891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK19	ENST00000368911.8	c.646+1227T>G		intron_variant	Intron 6 of 12	1	NM_015076.5	ENSP00000357907.3

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33631 AN: 152034 Hom.: 3912 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.221 AC: 33638 AN: 152150 Hom.: 3908 Cov.: 33 AF XY: 0.223 AC XY: 16589 AN XY: 74378

African (AFR) AF: 0.286 AC: 11864 AN: 41478

American (AMR) AF: 0.190 AC: 2904 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 898 AN: 3472

East Asian (EAS) AF: 0.171 AC: 887 AN: 5184

South Asian (SAS) AF: 0.236 AC: 1137 AN: 4824

European-Finnish (FIN) AF: 0.213 AC: 2257 AN: 10590

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13005 AN: 68004

Other (OTH) AF: 0.213 AC: 451 AN: 2116

Alfa AF: 0.211 Hom.: 559

Bravo AF: 0.221

Asia WGS AF: 0.165 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.81
PhyloP100		-0.13
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: rs2691180; hg19: chr6-110952006; COSMIC: COSV107397441;