chr2-201807870-C-G

Variant names:

• chr2-201807870-C-G
• rs997863043
• NM_001366386.2:c.286C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001366386.2(CDK15):​c.286C>G​(p.Pro96Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CDK15 NM_001366386.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40311062).

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.286C>G	p.Pro96Ala	missense	Exon 3 of 14	NP_001353315.1	Q96Q40-1
	CDK15	NM_001261435.1		c.286C>G	p.Pro96Ala	missense	Exon 3 of 14	NP_001248364.1	Q96Q40-5
	CDK15	NM_001261436.1		c.286C>G	p.Pro96Ala	missense	Exon 3 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.286C>G	p.Pro96Ala	missense	Exon 3 of 14	ENSP00000498608.2	Q96Q40-1
	CDK15	ENST00000450471.6	TSL:1	c.286C>G	p.Pro96Ala	missense	Exon 3 of 14	ENSP00000406472.2	Q96Q40-5
	CDK15	ENST00000434439.1	TSL:1	c.286C>G	p.Pro96Ala	missense	Exon 3 of 13	ENSP00000412775.1	Q96Q40-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461476 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727032

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111866

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

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	0.093
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	16
DANN	Uncertain	0.98
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.080
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.4
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.029	D
Sift4G	Benign	0.49	T
Vest4		0.33
MutPred		0.79		Gain of MoRF binding (P = 0.0483)
MVP		0.59
MPC		0.12
ClinPred		0.94	D
GERP RS		4.7
gMVP		0.28
Mutation Taster		=81/19	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: rs997863043; hg19: chr2-202672593;