10-60788210-A-G

Position:

chr10-60788210-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001786.5(CDK1):c.469A>G(p.Ile157Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000869 in 1,610,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

CDK1
NM_001786.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.16

Variant links:

Genes affected

CDK1 (HGNC:1722): (cyclin dependent kinase 1) The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is a catalytic subunit of the highly conserved protein kinase complex known as M-phase promoting factor (MPF), which is essential for G2/M phase transitions of eukaryotic cell cycle. Mitotic cyclins stably associate with this protein and function as regulatory subunits. The kinase activity of this protein is controlled by cyclin accumulation and destruction through the cell cycle. The phosphorylation and dephosphorylation of this protein also play important regulatory roles in cell cycle control. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2023]

CDK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08960897).

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CDK1	NM_001786.5 linkuse as main transcript	c.469A>G	p.Ile157Val	missense_variant	5/8	ENST00000395284.8	NP_001777.1
CDK1	NM_001320918.1 linkuse as main transcript	c.469A>G	p.Ile157Val	missense_variant	5/8		NP_001307847.1
CDK1	XM_005270303.4 linkuse as main transcript	c.469A>G	p.Ile157Val	missense_variant	5/8		XP_005270360.1
CDK1	NM_033379.5 linkuse as main transcript	c.318+2423A>G		intron_variant			NP_203698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK1	ENST00000395284.8 linkuse as main transcript	c.469A>G	p.Ile157Val	missense_variant	5/8	1	NM_001786.5	ENSP00000378699	P3	P06493-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000324

AC:

AN:

247244

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134214

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000236

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000891

AC:

AN:

1458424

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725464

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000180

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152100

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2022

The c.469A>G (p.I157V) alteration is located in exon 5 (coding exon 4) of the CDK1 gene. This alteration results from a A to G substitution at nucleotide position 469, causing the isoleucine (I) at amino acid position 157 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.57

DEOGEN2

Benign

0.010

T;T;T;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.090

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.24

.;N;.;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.27

N;N;N;.

REVEL

Benign

0.11

Sift

Benign

1.0

T;T;T;.

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

.;B;.;.

Vest4

0.088, 0.11, 0.095

MutPred

0.46

Gain of phosphorylation at T161 (P = 0.3195);Gain of phosphorylation at T161 (P = 0.3195);Gain of phosphorylation at T161 (P = 0.3195);Gain of phosphorylation at T161 (P = 0.3195);

MVP

0.54

MPC

0.88

ClinPred

0.074

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.19

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over