7-91079449-A-G

Position:

chr7-91079449-A-G

Variant summary

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

The NM_001287135.2(CDK14):c.1123A>G(p.Ser375Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000937 in 1,601,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

CDK14
NM_001287135.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.21

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=0.08670691).

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CDK14	NM_001287135.2 linkuse as main transcript	c.1123A>G	p.Ser375Gly	missense_variant	12/15	ENST00000380050.8	NP_001274064.1
CDK14	NM_012395.3 linkuse as main transcript	c.1069A>G	p.Ser357Gly	missense_variant	11/14		NP_036527.1
CDK14	NM_001287136.1 linkuse as main transcript	c.985A>G	p.Ser329Gly	missense_variant	11/14		NP_001274065.1
CDK14	NM_001287137.1 linkuse as main transcript	c.736A>G	p.Ser246Gly	missense_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.1123A>G	p.Ser375Gly	missense_variant	12/15	1	NM_001287135.2	ENSP00000369390	P4	O94921-1
CDK14	ENST00000265741.7 linkuse as main transcript	c.1069A>G	p.Ser357Gly	missense_variant	11/14	1		ENSP00000265741		O94921-2
CDK14	ENST00000406263.5 linkuse as main transcript	c.985A>G	p.Ser329Gly	missense_variant	11/14	1		ENSP00000385034	A1	O94921-3
CDK14	ENST00000436577.3 linkuse as main transcript	c.736A>G	p.Ser246Gly	missense_variant	10/13	2		ENSP00000398936

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000281

AC:

AN:

248860

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134488

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000383

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000897

AC:

AN:

1448790

Hom.:

Cov.:

AF XY:

0.00000693

AC XY:

AN XY:

721474

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000329

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000412

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

Jun 29, 2023

The c.1069A>G (p.S357G) alteration is located in exon 11 (coding exon 11) of the CDK14 gene. This alteration results from a A to G substitution at nucleotide position 1069, causing the serine (S) at amino acid position 357 to be replaced by a glycine (G). 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

Benign

0.072

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.089

T;.;.;.

Eigen

Benign

-0.15

Eigen_PC

Benign

0.022

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.83

T;T;T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.087

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.57

N;.;.;.

MutationTaster

Benign

0.79

D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Benign

0.084

Sift

Benign

0.26

T;T;T;T

Sift4G

Benign

0.37

T;T;T;T

Polyphen

0.0

B;B;.;B

Vest4

0.36

MutPred

0.35

Loss of disorder (P = 0.1158);.;.;.;

MVP

0.64

MPC

0.31

ClinPred

0.25

GERP RS

4.8

Varity_R

0.19

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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