7-90917691-A-G

Variant names:

• chr7-90917691-A-G
• rs1194624302
• NM_001287135.2:c.793A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001287135.2(CDK14):​c.793A>G​(p.Ser265Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S265C) 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: 9.32
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK14	NM_001287135.2	c.793A>G	p.Ser265Gly	missense_variant	Exon 8 of 15	ENST00000380050.8	NP_001274064.1
CDK14	NM_012395.3	c.739A>G	p.Ser247Gly	missense_variant	Exon 7 of 14		NP_036527.1
CDK14	NM_001287136.1	c.655A>G	p.Ser219Gly	missense_variant	Exon 7 of 14		NP_001274065.1
CDK14	NM_001287137.1	c.406A>G	p.Ser136Gly	missense_variant	Exon 6 of 13		NP_001274066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK14	ENST00000380050.8	c.793A>G	p.Ser265Gly	missense_variant	Exon 8 of 15	1	NM_001287135.2	ENSP00000369390.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;.;.;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.57	D;D;D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.49	N;.;.;.
PhyloP100		9.3
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0040	D;D;D;D
Sift4G	Uncertain	0.017	D;D;D;D
Polyphen		0.79	P;D;.;P
Vest4		0.48
MutPred		0.70		Loss of stability (P = 0.008);.;.;.;
MVP		0.79
MPC		0.81
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.55
gMVP		0.72
Mutation Taster		=20/80	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: rs1194624302; hg19: chr7-90547006;