rs2456773

Positions:

• chr10-60787260-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001786.5(CDK1):​c.319-800C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 151,950 control chromosomes in the GnomAD database, including 7,687 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7687 hom., cov: 32)
• Consequence: CDK1 NM_001786.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK1	NM_001786.5	c.319-800C>G		intron_variant		ENST00000395284.8	NP_001777.1
CDK1	NM_001320918.1	c.319-800C>G		intron_variant			NP_001307847.1
CDK1	NM_033379.5	c.318+1473C>G		intron_variant			NP_203698.1
CDK1	XM_005270303.4	c.319-800C>G		intron_variant			XP_005270360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK1	ENST00000395284.8	c.319-800C>G		intron_variant		1	NM_001786.5	ENSP00000378699	P3

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46854 AN: 151830 Hom.: 7689 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.315

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.309 AC: 46880 AN: 151950 Hom.: 7687 Cov.: 32 AF XY: 0.310 AC XY: 23029 AN XY: 74274

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.313

Alfa AF: 0.310 Hom.: 947

Bravo AF: 0.315

Asia WGS AF: 0.444 AC: 1545 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs2456773; hg19: chr10-62547018;