rs3735649

Positions:

• chr7-91118056-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001287135.2(CDK14):​c.1295-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0649 in 1,490,382 control chromosomes in the GnomAD database, including 5,794 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.077 (780 hom., cov: 32)
  • Exomes 𝑓: 0.064 (5014 hom.)
• Consequence: CDK14 NM_001287135.2 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.008685
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK14	NM_001287135.2	c.1295-9T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000380050.8
CDK14	NM_001287136.1	c.1157-9T>C		splice_polypyrimidine_tract_variant, intron_variant
CDK14	NM_001287137.1	c.908-9T>C		splice_polypyrimidine_tract_variant, intron_variant
CDK14	NM_012395.3	c.1241-9T>C		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK14	ENST00000380050.8	c.1295-9T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001287135.2	P4
CDK14	ENST00000265741.7	c.1241-9T>C		splice_polypyrimidine_tract_variant, intron_variant		1
CDK14	ENST00000406263.5	c.1157-9T>C		splice_polypyrimidine_tract_variant, intron_variant		1		A1
CDK14	ENST00000436577.3	c.908-9T>C		splice_polypyrimidine_tract_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 11754 AN: 152066 Hom.: 780 Cov.: 32

Gnomad AFR AF: 0.0950

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0447

Gnomad OTH AF: 0.0704

GnomAD3 exomes AF: 0.0865 AC: 21064 AN: 243436 Hom.: 1823 AF XY: 0.0884 AC XY: 11630 AN XY: 131512

Gnomad AFR exome AF: 0.0951

Gnomad AMR exome AF: 0.0313

Gnomad ASJ exome AF: 0.0622

Gnomad EAS exome AF: 0.329

Gnomad SAS exome AF: 0.167

Gnomad FIN exome AF: 0.0928

Gnomad NFE exome AF: 0.0440

Gnomad OTH exome AF: 0.0659

GnomAD4 exome AF: 0.0635 AC: 85027 AN: 1338198 Hom.: 5014 Cov.: 19 AF XY: 0.0660 AC XY: 44399 AN XY: 672326

Gnomad4 AFR exome AF: 0.0984

Gnomad4 AMR exome AF: 0.0316

Gnomad4 ASJ exome AF: 0.0619

Gnomad4 EAS exome AF: 0.324

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.0951

Gnomad4 NFE exome AF: 0.0438

Gnomad4 OTH exome AF: 0.0744

GnomAD4 genome AF: 0.0773 AC: 11766 AN: 152184 Hom.: 780 Cov.: 32 AF XY: 0.0818 AC XY: 6089 AN XY: 74394

Gnomad4 AFR AF: 0.0951

Gnomad4 AMR AF: 0.0464

Gnomad4 ASJ AF: 0.0660

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.0895

Gnomad4 NFE AF: 0.0447

Gnomad4 OTH AF: 0.0701

Alfa AF: 0.0518 Hom.: 429

Bravo AF: 0.0739

Asia WGS AF: 0.239 AC: 830 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0087
dbscSNV1_RF	Benign	0.048
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.20		Position offset: 9

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3735649; hg19: chr7-90747371;