Variant 7-90984204-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001287135.2(CDK14):c.1004T>C(p.Met335Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,536 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M335I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CDK14
NM_001287135.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.46

Variant links:

Genes affected

CDK14 (HGNC:8883): (cyclin dependent kinase 14) Enables cyclin binding activity and cyclin-dependent protein serine/threonine kinase activity. Involved in G2/M transition of mitotic cell cycle and regulation of canonical Wnt signaling pathway. Located in cytosol; nucleoplasm; and plasma membrane. Part of cytoplasmic cyclin-dependent protein kinase holoenzyme complex. [provided by Alliance of Genome Resources, Apr 2022]

CDK14 links:

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ACMG classification

Classification made for transcript

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
CDK14	NM_001287135.2 linkuse as main transcript	c.1004T>C	p.Met335Thr	missense_variant	10/15	ENST00000380050.8
CDK14	NM_012395.3 linkuse as main transcript	c.950T>C	p.Met317Thr	missense_variant	9/14
CDK14	NM_001287136.1 linkuse as main transcript	c.866T>C	p.Met289Thr	missense_variant	9/14
CDK14	NM_001287137.1 linkuse as main transcript	c.617T>C	p.Met206Thr	missense_variant	8/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK14	ENST00000380050.8 linkuse as main transcript	c.1004T>C	p.Met335Thr	missense_variant	10/15	1	NM_001287135.2	P4	O94921-1
CDK14	ENST00000265741.7 linkuse as main transcript	c.950T>C	p.Met317Thr	missense_variant	9/14	1			O94921-2
CDK14	ENST00000406263.5 linkuse as main transcript	c.866T>C	p.Met289Thr	missense_variant	9/14	1		A1	O94921-3
CDK14	ENST00000436577.3 linkuse as main transcript	c.617T>C	p.Met206Thr	missense_variant	8/13	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251230

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460536

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726714

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

The c.950T>C (p.M317T) alteration is located in exon 9 (coding exon 9) of the CDK14 gene. This alteration results from a T to C substitution at nucleotide position 950, causing the methionine (M) at amino acid position 317 to be replaced by a threonine (T). 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

Pathogenic

0.68

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Benign

0.93

DEOGEN2

Benign

0.049

T;.;.;.

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.86

D;D;D;D

M_CAP

Benign

0.020

MetaRNN

Uncertain

0.54

D;D;D;D

MetaSVM

Benign

-0.71

MutationAssessor

Benign

0.14

N;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Uncertain

0.39

Sift

Benign

0.50

T;T;T;T

Sift4G

Benign

0.67

T;T;T;T

Polyphen

0.84

P;B;.;P

Vest4

0.73

MutPred

0.29

Gain of methylation at K336 (P = 0.0239);.;.;.;

MVP

0.63

MPC

0.57

ClinPred

0.58

GERP RS

5.4

Varity_R

0.31

gMVP

0.77

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over