Genetic Variant NM_001287135.2:c.386T>C (chr7-90747697-T-C) – 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.386T>C(p.Phe129Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,966 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F129C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CDK14
NM_001287135.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.66

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:

Genome browser will be placed here

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.386T>C	p.Phe129Ser	missense_variant	Exon 4 of 15	ENST00000380050.8	NP_001274064.1	O94921-1
CDK14	NM_012395.3 link	c.332T>C	p.Phe111Ser	missense_variant	Exon 3 of 14		NP_036527.1	O94921-2
CDK14	NM_001287136.1 link	c.248T>C	p.Phe83Ser	missense_variant	Exon 3 of 14		NP_001274065.1	O94921-3
CDK14	NM_001287137.1 link	c.77+20885T>C		intron_variant	Intron 2 of 12		NP_001274066.1	O94921E7EUK8B4DK59

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK14	ENST00000380050.8 link	c.386T>C	p.Phe129Ser	missense_variant	Exon 4 of 15	1	NM_001287135.2	ENSP00000369390.3		O94921-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1444966

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718660

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32456

American (AMR)

AF:

0.00

AC:

AN:

40850

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25860

East Asian (EAS)

AF:

0.00

AC:

AN:

38634

South Asian (SAS)

AF:

0.00

AC:

AN:

82606

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1105788

Other (OTH)

AF:

0.00

AC:

AN:

59762

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

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

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

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

M_CAP

Benign

0.067

MetaRNN

Uncertain

0.63

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

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

0.55

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

PhyloP100

7.7

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-7.6

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

REVEL

Uncertain

0.36

Sift

Uncertain

0.0070

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

Sift4G

Pathogenic

0.0010

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

Polyphen

0.40, 1.0

.;.;.;.;B;.;D;.

Vest4

0.79, 0.88, 0.86

MutPred

0.33

.;.;.;.;Gain of phosphorylation at F129 (P = 0.0033);.;.;.;

MVP

0.81

MPC

1.5

ClinPred

1.0

GERP RS

5.9

Varity_R

0.86

gMVP

0.78

Mutation Taster

=27/73

disease causing

(source)

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

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

NM_001287135.2:c.386T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over