rs2448343

Positions:

• chr10-60779886-A-G
• chr10-60779886-A-T

Variant summary

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

The NM_001786.5(CDK1):​c.-25-255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,412 control chromosomes in the GnomAD database, including 27,361 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 0.60 (27361 hom., cov: 32)
• Consequence: CDK1 NM_001786.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK1	NM_001786.5	c.-25-255A>G		intron_variant		ENST00000395284.8	NP_001777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK1	ENST00000395284.8	c.-25-255A>G		intron_variant		1	NM_001786.5	ENSP00000378699.3

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90305 AN: 151296 Hom.: 27364 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.597 AC: 90347 AN: 151412 Hom.: 27361 Cov.: 32 AF XY: 0.601 AC XY: 44498 AN XY: 74026

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.680

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.619

Alfa AF: 0.598 Hom.: 12277

Bravo AF: 0.585

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.8
DANN	Benign	0.87

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: rs2448343; hg19: chr10-62539644;