Genetic Variant NM_001287135.2:c.274A>T (chr7-90726717-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001287135.2(CDK14):c.274A>T(p.Arg92Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,604 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CDK14
NM_001287135.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.22

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK14	NM_001287135.2 link	c.274A>T	p.Arg92Trp	missense_variant	Exon 3 of 15	ENST00000380050.8	NP_001274064.1	O94921-1
CDK14	NM_012395.3 link	c.220A>T	p.Arg74Trp	missense_variant	Exon 2 of 14		NP_036527.1	O94921-2
CDK14	NM_001287136.1 link	c.136A>T	p.Arg46Trp	missense_variant	Exon 2 of 14		NP_001274065.1	O94921-3
CDK14	NM_001287137.1 link	c.-19A>T		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.274A>T	p.Arg92Trp	missense_variant	Exon 3 of 15	1	NM_001287135.2	ENSP00000369390.3		O94921-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461604

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111804

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 11, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.220A>T (p.R74W) alteration is located in exon 2 (coding exon 2) of the CDK14 gene. This alteration results from a A to T substitution at nucleotide position 220, causing the arginine (R) at amino acid position 74 to be replaced by a tryptophan (W). 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

0.83

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

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

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

0.98

.;.;.;D;D;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.61

D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.55

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

PhyloP100

5.2

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.9

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

REVEL

Uncertain

0.30

Sift

Uncertain

0.0030

D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.014

D;D;D;D;D;D;D;D

Polyphen

0.88, 0.97

.;.;.;.;P;.;D;.

Vest4

0.81, 0.73, 0.73

MutPred

0.48

.;.;.;.;Loss of disorder (P = 0.0516);.;.;.;

MVP

0.79

MPC

0.87

ClinPred

0.95

GERP RS

4.5

Varity_R

0.18

gMVP

0.60

Mutation Taster

=11/89

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

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NM_001287135.2:c.274A>T

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