chr10-60792237-G-A

Variant names:

• chr10-60792237-G-A
• rs748366106
• NM_001786.5:c.743G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001786.5(CDK1):​c.743G>A​(p.Ser248Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,612,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: CDK1 NM_001786.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.52
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11447382).
• BS2: High AC in GnomAd4 at 5 AD gene.

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.743G>A	p.Ser248Asn	missense	Exon 7 of 8	NP_001777.1	P06493-1
	CDK1	NM_001320918.1		c.743G>A	p.Ser248Asn	missense	Exon 7 of 8	NP_001307847.1	P06493-1
	CDK1	NM_033379.5		c.572G>A	p.Ser191Asn	missense	Exon 6 of 7	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.743G>A	p.Ser248Asn	missense	Exon 7 of 8	ENSP00000378699.3	P06493-1
	CDK1	ENST00000448257.6	TSL:1	c.743G>A	p.Ser248Asn	missense	Exon 7 of 8	ENSP00000397973.2	A0A024QZP7
	CDK1	ENST00000373809.2	TSL:1	c.572G>A	p.Ser191Asn	missense	Exon 5 of 6	ENSP00000362915.2	P06493-2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152022 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250166 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000274 AC: 40 AN: 1460584 Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18 AN XY: 726578

African (AFR) AF: 0.0000300 AC: 1 AN: 33366

American (AMR) AF: 0.00 AC: 0 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26074

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000342 AC: 38 AN: 1111404

Other (OTH) AF: 0.0000166 AC: 1 AN: 60336

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152022 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74258

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Benign	0.67
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.093
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.5
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.058
Sift	Benign	0.66	T
Sift4G	Benign	0.67	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.28		Loss of disorder (P = 0.1013)
MVP		0.32
MPC		0.97
ClinPred		0.21	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.39
gMVP		0.45
Mutation Taster		=77/23	polymorphism

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: rs748366106; hg19: chr10-62551995;