chr2-201822878-C-A

Variant names:

• chr2-201822878-C-A
• rs1302097834
• NM_001366386.2:c.518C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001366386.2(CDK15):​c.518C>A​(p.Thr173Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000497 in 1,611,136 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CDK15 NM_001366386.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.66
• Publications: 0 publications found

Genes affected

CDK15 (HGNC:14434): (cyclin dependent kinase 15) Enables protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation and regulation of transcription involved in G1/S transition of mitotic cell cycle. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366386.2. 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
	CDK15	NM_001366386.2	MANE Select	c.518C>A	p.Thr173Lys	missense	Exon 5 of 14	NP_001353315.1	Q96Q40-1
	CDK15	NM_001261435.1		c.518C>A	p.Thr173Lys	missense	Exon 5 of 14	NP_001248364.1	Q96Q40-5
	CDK15	NM_001261436.1		c.518C>A	p.Thr173Lys	missense	Exon 5 of 13	NP_001248365.1	Q96Q40-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK15	ENST00000652192.3	MANE Select	c.518C>A	p.Thr173Lys	missense	Exon 5 of 14	ENSP00000498608.2	Q96Q40-1
	CDK15	ENST00000450471.6	TSL:1	c.518C>A	p.Thr173Lys	missense	Exon 5 of 14	ENSP00000406472.2	Q96Q40-5
	CDK15	ENST00000434439.1	TSL:1	c.518C>A	p.Thr173Lys	missense	Exon 5 of 13	ENSP00000412775.1	Q96Q40-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 33

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

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1458952 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 725966

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000631 AC: 7 AN: 1109498

Other (OTH) AF: 0.00 AC: 0 AN: 60276

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74344

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
Eigen	Benign	0.015
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.11	N
PhyloP100		4.7
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.28
Sift	Benign	0.41	T
Sift4G	Benign	1.0	T
Vest4		0.69
MutPred		0.49		Gain of ubiquitination at T173 (P = 0.0311)
MVP		0.60
MPC		0.31
ClinPred		0.84	D
GERP RS		3.6
gMVP		0.57
Mutation Taster		=67/33	polymorphism

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: rs1302097834; hg19: chr2-202687601;