rs2456778

Positions:

• chr10-60792132-A-G
• chr10-60792132-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001786.5(CDK1):​c.654-16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDK1 NM_001786.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491

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	Protein	UniProt
CDK1	NM_001786.5	c.654-16A>G		intron_variant		ENST00000395284.8	NP_001777.1
CDK1	NM_001320918.1	c.654-16A>G		intron_variant			NP_001307847.1
CDK1	NM_033379.5	c.483-16A>G		intron_variant			NP_203698.1
CDK1	XM_005270303.4	c.654-16A>G		intron_variant			XP_005270360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK1	ENST00000395284.8	c.654-16A>G		intron_variant		1	NM_001786.5	ENSP00000378699.3
CDK1	ENST00000448257.6	c.654-16A>G		intron_variant		1		ENSP00000397973.2
CDK1	ENST00000373809.2	c.483-16A>G		intron_variant		1		ENSP00000362915.2
CDK1	ENST00000316629.8	c.483-16A>G		intron_variant		5		ENSP00000325970.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Pathogenic	28
DANN	Benign	0.55
FATHMM_MKL	Benign	0.14	N
GERP RS		1.1
BranchPoint Hunter		4.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.91		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.91		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2456778; hg19: chr10-62551890;