rs376270298

Variant names:

• chr7-90917698-C-A
• rs376270298
• NM_001287135.2:c.800C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-90917698-C-A
• chr7-90917698-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001287135.2(CDK14):​c.800C>A​(p.Thr267Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign 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. T267M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CDK14 NM_001287135.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12572122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK14	NM_001287135.2	c.800C>A	p.Thr267Lys	missense_variant	Exon 8 of 15	ENST00000380050.8	NP_001274064.1
CDK14	NM_012395.3	c.746C>A	p.Thr249Lys	missense_variant	Exon 7 of 14		NP_036527.1
CDK14	NM_001287136.1	c.662C>A	p.Thr221Lys	missense_variant	Exon 7 of 14		NP_001274065.1
CDK14	NM_001287137.1	c.413C>A	p.Thr138Lys	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.800C>A	p.Thr267Lys	missense_variant	Exon 8 of 15	1	NM_001287135.2	ENSP00000369390.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461020 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726848

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111406

Other (OTH) AF: 0.00 AC: 0 AN: 60358

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.050	T;.;.;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.079
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.36	N;.;.;.
PhyloP100		1.3
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.093
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.028	B;P;.;B
Vest4		0.36
MutPred		0.35		Gain of ubiquitination at T267 (P = 0.0121);.;.;.;
MVP		0.37
MPC		0.43
ClinPred		0.89	D
GERP RS		4.6
Varity_R		0.20
gMVP		0.70
Mutation Taster		=34/66	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs376270298; hg19: chr7-90547013; COSMIC: COSV56049079;