10-60785677-C-G

Variant names:

• chr10-60785677-C-G
• rs780626115
• NM_001786.5:c.208C>G

Variant summary

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

The NM_001786.5(CDK1):​c.208C>G​(p.Leu70Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK1 NM_001786.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.87
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001786.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK1	NM_001786.5	MANE Select	c.208C>G	p.Leu70Val	missense	Exon 4 of 8	NP_001777.1	P06493-1
	CDK1	NM_001320918.1		c.208C>G	p.Leu70Val	missense	Exon 4 of 8	NP_001307847.1	P06493-1
	CDK1	NM_033379.5		c.208C>G	p.Leu70Val	missense	Exon 4 of 7	NP_203698.1	P06493-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK1	ENST00000395284.8	TSL:1 MANE Select	c.208C>G	p.Leu70Val	missense	Exon 4 of 8	ENSP00000378699.3	P06493-1
	CDK1	ENST00000448257.6	TSL:1	c.208C>G	p.Leu70Val	missense	Exon 4 of 8	ENSP00000397973.2	A0A024QZP7
	CDK1	ENST00000373809.2	TSL:1	c.208C>G	p.Leu70Val	missense	Exon 3 of 6	ENSP00000362915.2	P06493-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Benign	0.60
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		7.9
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.47	N
REVEL	Uncertain	0.29
Sift	Benign	0.89	T
Sift4G	Benign	0.65	T
Polyphen		0.033	B
Vest4		0.60
MutPred		0.49		Loss of stability (P = 0.1532)
MVP		0.85
MPC		1.2
ClinPred		0.91	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.50
Mutation Taster		=28/72	disease causing

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

Other links and lift over

dbSNP: rs780626115; hg19: chr10-62545435;