7-90726802-G-C

Variant names:

• chr7-90726802-G-C
• rs138436598
• NM_001287135.2:c.359G>C

Variant summary

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

The NM_001287135.2(CDK14):​c.359G>C​(p.Ser120Thr) variant causes a missense change involving the alteration of a conserved nucleotide. 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. S120N) 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: 9.13
• Publications: 1 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, 0.782

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK14	NM_001287135.2	c.359G>C	p.Ser120Thr	missense_variant	Exon 3 of 15	ENST00000380050.8	NP_001274064.1
CDK14	NM_012395.3	c.305G>C	p.Ser102Thr	missense_variant	Exon 2 of 14		NP_036527.1
CDK14	NM_001287136.1	c.221G>C	p.Ser74Thr	missense_variant	Exon 2 of 14		NP_001274065.1
CDK14	NM_001287137.1	c.67G>C	p.Ala23Pro	missense_variant	Exon 2 of 13		NP_001274066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK14	ENST00000380050.8	c.359G>C	p.Ser120Thr	missense_variant	Exon 3 of 15	1	NM_001287135.2	ENSP00000369390.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	27
DANN	Uncertain	0.98
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.76	T
PhyloP100		9.1
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.52
Sift	Benign	0.046	D
Sift4G	Uncertain	0.013	D
Polyphen		0.81	P
Vest4		0.55
MutPred		0.74		Gain of glycosylation at A23 (P = 0.0085);
MVP		0.78
ClinPred		0.64	D
GERP RS		5.5
Varity_R		0.22
Mutation Taster		=32/68	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: rs138436598; hg19: chr7-90356116;