chr7-90984162-T-A

Variant names:

• chr7-90984162-T-A
• rs1795315572
• NM_001287135.2:c.962T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001287135.2(CDK14):​c.962T>A​(p.Ile321Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,070 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I321T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CDK14 NM_001287135.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.46
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.914

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK14	NM_001287135.2	c.962T>A	p.Ile321Asn	missense_variant	Exon 10 of 15	ENST00000380050.8	NP_001274064.1
CDK14	NM_012395.3	c.908T>A	p.Ile303Asn	missense_variant	Exon 9 of 14		NP_036527.1
CDK14	NM_001287136.1	c.824T>A	p.Ile275Asn	missense_variant	Exon 9 of 14		NP_001274065.1
CDK14	NM_001287137.1	c.575T>A	p.Ile192Asn	missense_variant	Exon 8 of 13		NP_001274066.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK14	ENST00000380050.8	c.962T>A	p.Ile321Asn	missense_variant	Exon 10 of 15	1	NM_001287135.2	ENSP00000369390.3
CDK14	ENST00000265741.7	c.908T>A	p.Ile303Asn	missense_variant	Exon 9 of 14	1		ENSP00000265741.3
CDK14	ENST00000406263.5	c.824T>A	p.Ile275Asn	missense_variant	Exon 9 of 14	1		ENSP00000385034.1
CDK14	ENST00000436577.3	c.575T>A	p.Ile192Asn	missense_variant	Exon 8 of 13	2		ENSP00000398936.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457070 Hom.: 0 Cov.: 28 AF XY: 0.00000276 AC XY: 2 AN XY: 725218

African (AFR) AF: 0.00 AC: 0 AN: 33380

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.00 AC: 0 AN: 86140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107722

Other (OTH) AF: 0.00 AC: 0 AN: 60210

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T;.;.;.
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D;D;D
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.91	D;D;D;D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Pathogenic	4.2	H;.;.;.
PhyloP100		7.5
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-6.5	D;D;D;D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;.;D
Vest4		0.97
MutPred		0.69		Loss of stability (P = 0.1441);.;.;.;
MVP		0.78
MPC		1.5
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.93
gMVP		0.98
Mutation Taster		=9/91	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1795315572; hg19: chr7-90613477;