Variant chr7-90747744-T-A 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.433T>A(p.Ser145Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,444,436 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CDK14
NM_001287135.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.66

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	Protein
CDK14	NM_001287135.2 linkuse as main transcript	c.433T>A	p.Ser145Thr	missense_variant	4/15	ENST00000380050.8	NP_001274064.1
CDK14	NM_012395.3 linkuse as main transcript	c.379T>A	p.Ser127Thr	missense_variant	3/14		NP_036527.1
CDK14	NM_001287136.1 linkuse as main transcript	c.295T>A	p.Ser99Thr	missense_variant	3/14		NP_001274065.1
CDK14	NM_001287137.1 linkuse as main transcript	c.77+20932T>A		intron_variant			NP_001274066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK14	ENST00000380050.8 linkuse as main transcript	c.433T>A	p.Ser145Thr	missense_variant	4/15	1	NM_001287135.2	ENSP00000369390	P4	O94921-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1444436

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

718130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000244

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.379T>A (p.S127T) alteration is located in exon 3 (coding exon 3) of the CDK14 gene. This alteration results from a T to A substitution at nucleotide position 379, causing the serine (S) at amino acid position 127 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

0.64

BayesDel_addAF

Uncertain

0.087

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Benign

0.92

DEOGEN2

Benign

0.027

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

Eigen

Benign

0.038

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.43

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

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.59

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

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.12

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

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.28

N;N;N;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.73

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

Sift4G

Benign

0.95

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

Polyphen

0.96, 0.32

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

Vest4

0.66, 0.79, 0.78

MutPred

0.80

.;.;.;.;Loss of phosphorylation at S145 (P = 0.0541);.;.;

MVP

0.67

MPC

0.33

ClinPred

0.77

GERP RS

5.9

Varity_R

0.23

gMVP

0.54

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over