2-201835736-C-T

Position:

• chr2-201835736-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001366386.2(CDK15):​c.824C>T​(p.Thr275Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: CDK15 NM_001366386.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.83

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]

CDK15 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK15	NM_001366386.2	c.824C>T	p.Thr275Ile	missense_variant	8/14	ENST00000652192.3	NP_001353315.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK15	ENST00000652192.3	c.824C>T	p.Thr275Ile	missense_variant	8/14		NM_001366386.2	ENSP00000498608.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 21, 2024

The c.671C>T (p.T224I) alteration is located in exon 8 (coding exon 7) of the CDK15 gene. This alteration results from a C to T substitution at nucleotide position 671, causing the threonine (T) at amino acid position 224 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	.;D;D;D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.3	.;.;L;L
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.1	D;D;D;D
REVEL	Uncertain	0.58
Sift	Benign	0.031	D;D;D;D
Sift4G	Benign	0.082	T;T;D;T
Vest4		0.73
MutPred		0.48		.;.;Loss of disorder (P = 0.0474);Loss of disorder (P = 0.0474);
MVP		0.73
MPC		0.24
ClinPred		0.99	D
GERP RS		5.6
gMVP		0.38

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-202700459;