NM_001287135.2:c.577A>T

Variant names:

• chr7-90863207-A-T
• rs146138173
• NM_001287135.2:c.577A>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001287135.2(CDK14):​c.577A>T​(p.Ile193Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I193V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK14 NM_001287135.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.97
• Publications: 2 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.748

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK14	NM_001287135.2	c.577A>T	p.Ile193Leu	missense_variant	Exon 6 of 15	ENST00000380050.8	NP_001274064.1
CDK14	NM_012395.3	c.523A>T	p.Ile175Leu	missense_variant	Exon 5 of 14		NP_036527.1
CDK14	NM_001287136.1	c.439A>T	p.Ile147Leu	missense_variant	Exon 5 of 14		NP_001274065.1
CDK14	NM_001287137.1	c.190A>T	p.Ile64Leu	missense_variant	Exon 4 of 13		NP_001274066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK14	ENST00000380050.8	c.577A>T	p.Ile193Leu	missense_variant	Exon 6 of 15	1	NM_001287135.2	ENSP00000369390.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.75	D;D;D;D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.3	M;.;.;.
PhyloP100		7.0
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Uncertain	0.44
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		0.25	B;P;.;B
Vest4		0.64
MutPred		0.74		Loss of methylation at K189 (P = 0.0556);.;.;.;
MVP		0.82
MPC		1.1
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.59
gMVP		0.72
Mutation Taster		=44/56	disease causing

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

Other links and lift over

dbSNP: rs146138173; hg19: chr7-90492522;