7-90726615-G-A

Position:

• chr7-90726615-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001287135.2(CDK14):​c.172G>A​(p.Val58Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK14 NM_001287135.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.09

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37252948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK14	NM_001287135.2	c.172G>A	p.Val58Met	missense_variant	3/15	ENST00000380050.8
CDK14	NM_012395.3	c.118G>A	p.Val40Met	missense_variant	2/14
CDK14	NM_001287136.1	c.34G>A	p.Val12Met	missense_variant	2/14
CDK14	NM_001287137.1	c.-121G>A		5_prime_UTR_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK14	ENST00000380050.8	c.172G>A	p.Val58Met	missense_variant	3/15	1	NM_001287135.2	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2023

The c.118G>A (p.V40M) 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 118, causing the valine (V) at amino acid position 40 to be replaced by a methionine (M). 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	0.087
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.067	T;T;T;T;T;T;.;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.37	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.40	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.90	N;N;N;N;N;N;N;N
REVEL	Benign	0.22
Sift	Benign	0.033	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D;T;D;D;D
Polyphen		0.95, 0.97	.;.;.;.;P;.;D;.
Vest4		0.47, 0.42, 0.46
MutPred		0.20		.;.;.;.;Gain of disorder (P = 0.097);.;.;.;
MVP		0.81
MPC		1.1
ClinPred		0.72	D
GERP RS		5.7
Varity_R		0.14
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-90355929;