Genetic Variant NM_001287135.2:c.943A>G (chr7-90955813-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001287135.2(CDK14):c.943A>G(p.Met315Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,612,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

CDK14
NM_001287135.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.30

Publications

1 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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 62 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK14	NM_001287135.2 link	c.943A>G	p.Met315Val	missense_variant	Exon 9 of 15	ENST00000380050.8	NP_001274064.1	O94921-1
CDK14	NM_012395.3 link	c.889A>G	p.Met297Val	missense_variant	Exon 8 of 14		NP_036527.1	O94921-2
CDK14	NM_001287136.1 link	c.805A>G	p.Met269Val	missense_variant	Exon 8 of 14		NP_001274065.1	O94921-3
CDK14	NM_001287137.1 link	c.556A>G	p.Met186Val	missense_variant	Exon 7 of 13		NP_001274066.1	O94921E7EUK8B4DK59

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK14	ENST00000380050.8 link	c.943A>G	p.Met315Val	missense_variant	Exon 9 of 15	1	NM_001287135.2	ENSP00000369390.3		O94921-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000478

AC:

AN:

250854

AF XY:

0.0000369

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000794

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000424

AC:

AN:

1460696

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

726704

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.000112

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000495

AC:

AN:

1111176

Other (OTH)

AF:

0.0000332

AC:

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41438

American (AMR)

AF:

0.0000656

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000302

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 03, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.889A>G (p.M297V) alteration is located in exon 8 (coding exon 8) of the CDK14 gene. This alteration results from a A to G substitution at nucleotide position 889, causing the methionine (M) at amino acid position 297 to be replaced by a valine (V). 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

0.24

BayesDel_addAF

Uncertain

0.086

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.094

T;.;.;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.68

D;D;D;D

MetaSVM

Benign

-0.74

MutationAssessor

Benign

-0.41

N;.;.;.

PhyloP100

9.3

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Uncertain

0.29

Sift

Uncertain

0.024

D;D;D;D

Sift4G

Uncertain

0.045

D;T;T;T

Polyphen

0.94

P;B;.;P

Vest4

0.80

MVP

0.84

MPC

0.86

ClinPred

0.30

GERP RS

6.1

Varity_R

0.37

gMVP

0.82

Mutation Taster

=14/86

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_001287135.2:c.943A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over