chr10-60793917-A-G

Position:

chr10-60793917-A-G

Variant summary

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

The ENST00000395284.8(CDK1):c.836A>G(p.Lys279Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000384 in 1,564,460 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: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

CDK1
ENST00000395284.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05

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=0.105571985).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CDK1	NM_001786.5 linkuse as main transcript	c.836A>G	p.Lys279Arg	missense_variant	8/8	ENST00000395284.8	NP_001777.1
CDK1	NM_001320918.1 linkuse as main transcript	c.836A>G	p.Lys279Arg	missense_variant	8/8		NP_001307847.1
CDK1	NM_033379.5 linkuse as main transcript	c.665A>G	p.Lys222Arg	missense_variant	7/7		NP_203698.1
CDK1	XM_005270303.4 linkuse as main transcript	c.836A>G	p.Lys279Arg	missense_variant	8/8		XP_005270360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK1	ENST00000395284.8 linkuse as main transcript	c.836A>G	p.Lys279Arg	missense_variant	8/8	1	NM_001786.5	ENSP00000378699	P3	P06493-1
CDK1	ENST00000448257.6 linkuse as main transcript	c.836A>G	p.Lys279Arg	missense_variant	8/8	1		ENSP00000397973	A1
CDK1	ENST00000373809.2 linkuse as main transcript	c.665A>G	p.Lys222Arg	missense_variant	6/6	1		ENSP00000362915		P06493-2
CDK1	ENST00000316629.8 linkuse as main transcript	c.665A>G	p.Lys222Arg	missense_variant	7/7	5		ENSP00000325970		P06493-2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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:

0.00000967

AC:

AN:

206882

Hom.:

AF XY:

0.00000882

AC XY:

AN XY:

113366

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000144

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:

0.00000354

AC:

AN:

1412414

Hom.:

Cov.:

AF XY:

0.00000427

AC XY:

AN XY:

702962

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000827

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.15e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152046

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

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

Feb 17, 2024

The c.836A>G (p.K279R) alteration is located in exon 8 (coding exon 7) of the CDK1 gene. This alteration results from a A to G substitution at nucleotide position 836, causing the lysine (K) at amino acid position 279 to be replaced by an arginine (R). 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

0.088

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

.;T;T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.88

D;D;D;.

M_CAP

Benign

0.0051

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.65

.;N;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.56

N;N;N;N

REVEL

Benign

0.027

Sift

Benign

0.38

T;T;T;T

Sift4G

Benign

0.26

T;T;T;T

Polyphen

0.010

B;B;.;B

Vest4

0.15

MutPred

0.37

.;Loss of ubiquitination at K279 (P = 0.0199);Loss of ubiquitination at K279 (P = 0.0199);.;

MVP

0.53

MPC

0.86

ClinPred

0.25

GERP RS

6.0

Varity_R

0.38

gMVP

0.34

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