chr7-90790574-G-A

Variant names:

• chr7-90790574-G-A
• rs751932807
• NM_001287135.2:c.466G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_001287135.2(CDK14):​c.466G>A​(p.Val156Ile) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000618 in 1,455,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: CDK14 NM_001287135.2 missense, splice_region
• Scores: Splicing: ADA: 0.9869
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.62
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK14	NM_001287135.2	c.466G>A	p.Val156Ile	missense_variant, splice_region_variant	Exon 5 of 15	ENST00000380050.8	NP_001274064.1
CDK14	NM_012395.3	c.412G>A	p.Val138Ile	missense_variant, splice_region_variant	Exon 4 of 14		NP_036527.1
CDK14	NM_001287136.1	c.328G>A	p.Val110Ile	missense_variant, splice_region_variant	Exon 4 of 14		NP_001274065.1
CDK14	NM_001287137.1	c.79G>A	p.Val27Ile	missense_variant, splice_region_variant	Exon 3 of 13		NP_001274066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK14	ENST00000380050.8	c.466G>A	p.Val156Ile	missense_variant, splice_region_variant	Exon 5 of 15	1	NM_001287135.2	ENSP00000369390.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 250160 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000176

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000618 AC: 9 AN: 1455396 Hom.: 0 Cov.: 28 AF XY: 0.00000414 AC XY: 3 AN XY: 724330

African (AFR) AF: 0.00 AC: 0 AN: 33302

American (AMR) AF: 0.000203 AC: 9 AN: 44310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39524

South Asian (SAS) AF: 0.00 AC: 0 AN: 85844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107200

Other (OTH) AF: 0.00 AC: 0 AN: 60140

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.412G>A (p.V138I) alteration is located in exon 4 (coding exon 4) of the CDK14 gene. This alteration results from a G to A substitution at nucleotide position 412, causing the valine (V) at amino acid position 138 to be replaced by an isoleucine (I). 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	0.15
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T;T;T;T;T;.;.;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.77	.;.;.;T;T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.26	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.78	.;.;.;.;N;.;.;.
PhyloP100		8.6
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.27	N;N;N;N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.46	T;T;T;T;T;T;T;T
Sift4G	Benign	0.76	T;T;T;T;T;T;T;T
Polyphen		0.43, 0.052, 0.29	.;.;.;.;B;B;.;B
Vest4		0.26, 0.25, 0.24, 0.21
MutPred		0.39		.;.;.;.;Loss of methylation at K155 (P = 0.0678);.;.;.;
MVP		0.51
MPC		0.30
ClinPred		0.24	T
GERP RS		5.8
Varity_R		0.054
gMVP		0.33
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.73
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

Other links and lift over

dbSNP: rs751932807; hg19: chr7-90419889;