rs2448343

Variant names:

• chr10-60779886-A-G
• rs2448343
• NM_001786.5:c.-25-255A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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: Benign. The variant received -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.

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.-25-255A>G		intron	N/A	NP_001777.1	P06493-1
	CDK1	NM_001320918.1		c.-25-255A>G		intron	N/A	NP_001307847.1	P06493-1
	CDK1	NM_033379.5		c.-25-255A>G		intron	N/A	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.-25-255A>G		intron	N/A	ENSP00000378699.3	P06493-1
	CDK1	ENST00000448257.6	TSL:1	c.-25-255A>G		intron	N/A	ENSP00000397973.2	A0A024QZP7
	CDK1	ENST00000856536.1		c.-25-255A>G		intron	N/A	ENSP00000526595.1

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

African (AFR) AF: 0.482 AC: 19945 AN: 41376

American (AMR) AF: 0.621 AC: 9474 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2092 AN: 3454

East Asian (EAS) AF: 0.762 AC: 3931 AN: 5158

South Asian (SAS) AF: 0.654 AC: 3126 AN: 4782

European-Finnish (FIN) AF: 0.680 AC: 7152 AN: 10522

Middle Eastern (MID) AF: 0.651 AC: 190 AN: 292

European-Non Finnish (NFE) AF: 0.631 AC: 42647 AN: 67562

Other (OTH) AF: 0.619 AC: 1306 AN: 2110

Alfa AF: 0.602 Hom.: 17756

Bravo AF: 0.585

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.8
DANN	Benign	0.87
PhyloP100		-0.056
PromoterAI		0.0068	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs2448343; hg19: chr10-62539644;