10-60785677-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDK1	NM_001786.5	c.208C>G	p.Leu70Val	missense_variant	4/8	ENST00000395284.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDK1	ENST00000395284.8	c.208C>G	p.Leu70Val	missense_variant	4/8	1	NM_001786.5	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.208C>G (p.L70V) alteration is located in exon 4 (coding exon 3) of the CDK1 gene. This alteration results from a C to G substitution at nucleotide position 208, causing the leucine (L) at amino acid position 70 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	0.15
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
Cadd	Benign	22
Dann	Benign	0.60
DEOGEN2	Benign	0.011	T;.;T;T;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;.
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.50	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.47	N;N;N;N;.;N
REVEL	Uncertain	0.29
Sift	Benign	0.89	T;T;T;T;.;T
Sift4G	Benign	0.65	T;T;T;T;T;T
Polyphen		0.033, 0.041	.;B;B;.;.;B
Vest4		0.60, 0.60, 0.60, 0.61
MutPred		0.49		Loss of stability (P = 0.1532);Loss of stability (P = 0.1532);Loss of stability (P = 0.1532);Loss of stability (P = 0.1532);Loss of stability (P = 0.1532);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-62545435;