Variant 7-90726802-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001287135.2(CDK14):c.359G>A(p.Ser120Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000457 in 1,613,350 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 1 hom. )

Consequence

CDK14
NM_001287135.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.13

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21692297).

BS2

High AC in GnomAd4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CDK14	NM_001287135.2 linkuse as main transcript	c.359G>A	p.Ser120Asn	missense_variant	3/15	ENST00000380050.8
CDK14	NM_012395.3 linkuse as main transcript	c.305G>A	p.Ser102Asn	missense_variant	2/14
CDK14	NM_001287136.1 linkuse as main transcript	c.221G>A	p.Ser74Asn	missense_variant	2/14
CDK14	NM_001287137.1 linkuse as main transcript	c.67G>A	p.Ala23Thr	missense_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK14	ENST00000380050.8 linkuse as main transcript	c.359G>A	p.Ser120Asn	missense_variant	3/15	1	NM_001287135.2	P4	O94921-1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

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:

0.000515

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000279

AC:

AN:

247630

Hom.:

AF XY:

0.000261

AC XY:

AN XY:

134270

show subpopulations

Gnomad AFR exome

AF:

0.000188

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000577

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000474

AC:

693

AN:

1461224

Hom.:

Cov.:

AF XY:

0.000461

AC XY:

335

AN XY:

726916

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000564

Gnomad4 NFE exome

AF:

0.000595

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000289

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000498

Hom.:

Bravo

AF:

0.000314

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000313

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

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 27, 2022

The c.305G>A (p.S102N) alteration is located in exon 2 (coding exon 2) of the CDK14 gene. This alteration results from a G to A substitution at nucleotide position 305, causing the serine (S) at amino acid position 102 to be replaced by an asparagine (N). 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

Uncertain

0.55

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

0.98

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.48

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.68

MutationTaster

Benign

1.0

D;D;D;D

PROVEAN

Benign

-0.76

REVEL

Uncertain

0.37

Sift

Uncertain

0.0040

Sift4G

Pathogenic

0.0010

Polyphen

0.28

Vest4

0.47

MVP

0.86

ClinPred

0.031

GERP RS

5.5

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