Variant 7-91079434-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001287135.2(CDK14):c.1108C>A(p.Arg370Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000063 in 1,428,344 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

CDK14
NM_001287135.2 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69

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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CDK14	NM_001287135.2 linkuse as main transcript	c.1108C>A	p.Arg370Ser	missense_variant, splice_region_variant	12/15	ENST00000380050.8	NP_001274064.1
CDK14	NM_012395.3 linkuse as main transcript	c.1054C>A	p.Arg352Ser	missense_variant, splice_region_variant	11/14		NP_036527.1
CDK14	NM_001287136.1 linkuse as main transcript	c.970C>A	p.Arg324Ser	missense_variant, splice_region_variant	11/14		NP_001274065.1
CDK14	NM_001287137.1 linkuse as main transcript	c.721C>A	p.Arg241Ser	missense_variant, splice_region_variant	10/13		NP_001274066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK14	ENST00000380050.8 linkuse as main transcript	c.1108C>A	p.Arg370Ser	missense_variant, splice_region_variant	12/15	1	NM_001287135.2	ENSP00000369390	P4	O94921-1
CDK14	ENST00000265741.7 linkuse as main transcript	c.1054C>A	p.Arg352Ser	missense_variant, splice_region_variant	11/14	1		ENSP00000265741		O94921-2
CDK14	ENST00000406263.5 linkuse as main transcript	c.970C>A	p.Arg324Ser	missense_variant, splice_region_variant	11/14	1		ENSP00000385034	A1	O94921-3
CDK14	ENST00000436577.3 linkuse as main transcript	c.721C>A	p.Arg241Ser	missense_variant, splice_region_variant	10/13	2		ENSP00000398936

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000333

AC:

AN:

239908

Hom.:

AF XY:

0.0000231

AC XY:

AN XY:

129620

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000222

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:

0.00

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.00000630

AC:

AN:

1428344

Hom.:

Cov.:

AF XY:

0.00000422

AC XY:

AN XY:

711484

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000192

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000165

AC:

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

Nov 23, 2021

The c.1054C>A (p.R352S) alteration is located in exon 11 (coding exon 11) of the CDK14 gene. This alteration results from a C to A substitution at nucleotide position 1054, causing the arginine (R) at amino acid position 352 to be replaced by a serine (S). 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

0.45

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Benign

0.90

DEOGEN2

Benign

0.072

T;.;.;.

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.80

T;T;T;T

M_CAP

Benign

0.0093

MetaRNN

Uncertain

0.61

D;D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.090

N;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.28

Sift

Benign

0.45

T;T;T;T

Sift4G

Benign

0.78

T;T;T;T

Polyphen

0.99

D;B;.;D

Vest4

0.80

MutPred

0.66

Loss of MoRF binding (P = 0.0376);.;.;.;

MVP

0.73

MPC

0.42

ClinPred

0.30

GERP RS

4.8

Varity_R

0.50

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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