Genetic Variant CDK14:p.Thr79Ala (chr7-90726678-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001287135.2(CDK14):c.235A>G(p.Thr79Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

CDK14
NM_001287135.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.34

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13979).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK14	NM_001287135.2 link	c.235A>G	p.Thr79Ala	missense_variant	Exon 3 of 15	ENST00000380050.8	NP_001274064.1	O94921-1
CDK14	NM_012395.3 link	c.181A>G	p.Thr61Ala	missense_variant	Exon 2 of 14		NP_036527.1	O94921-2
CDK14	NM_001287136.1 link	c.97A>G	p.Thr33Ala	missense_variant	Exon 2 of 14		NP_001274065.1	O94921-3
CDK14	NM_001287137.1 link	c.-58A>G		5_prime_UTR_variant	Exon 2 of 13		NP_001274066.1	O94921E7EUK8B4DK59

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK14	ENST00000380050.8 link	c.235A>G	p.Thr79Ala	missense_variant	Exon 3 of 15	1	NM_001287135.2	ENSP00000369390.3		O94921-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

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

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 10, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.181A>G (p.T61A) alteration is located in exon 2 (coding exon 2) of the CDK14 gene. This alteration results from a A to G substitution at nucleotide position 181, causing the threonine (T) at amino acid position 61 to be replaced by an alanine (A). 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

Benign

0.059

BayesDel_addAF

Benign

0.0025

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.065

T;T;T;T;T;T;.;.

Eigen

Benign

-0.062

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.80

.;.;.;T;T;T;T;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.14

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.34

.;.;.;.;N;.;.;.

PhyloP100

5.3

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.4

N;N;N;N;N;D;N;N

REVEL

Benign

0.069

Sift

Uncertain

0.0090

D;D;D;D;T;D;D;D

Sift4G

Uncertain

0.024

D;D;D;D;T;T;D;T

Polyphen

0.0080, 0.013

.;.;.;.;B;.;B;.

Vest4

0.33, 0.27, 0.28

MutPred

0.079

.;.;.;.;Loss of phosphorylation at T79 (P = 0.0571);.;.;.;

MVP

0.82

MPC

0.34

ClinPred

0.69

GERP RS

5.9

Varity_R

0.12

gMVP

0.22

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

7-90726678-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over