rs2456772

Variant names:

• chr10-60788340-G-A
• rs2456772
• NM_001786.5:c.489+110G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-60788340-G-A
• chr10-60788340-G-C
• chr10-60788340-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001786.5(CDK1):​c.489+110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000352 in 568,284 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: CDK1 NM_001786.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.676
• Publications: 5 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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.489+110G>A		intron	N/A	NP_001777.1	P06493-1
	CDK1	NM_001320918.1		c.489+110G>A		intron	N/A	NP_001307847.1	P06493-1
	CDK1	NM_033379.5		c.318+2553G>A		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.489+110G>A		intron	N/A	ENSP00000378699.3	P06493-1
	CDK1	ENST00000448257.6	TSL:1	c.493+106G>A		intron	N/A	ENSP00000397973.2	A0A024QZP7
	CDK1	ENST00000373809.2	TSL:1	c.318+2553G>A		intron	N/A	ENSP00000362915.2	P06493-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000352 AC: 2 AN: 568284 Hom.: 0 AF XY: 0.00000695 AC XY: 2 AN XY: 287638

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 13824

American (AMR) AF: 0.00 AC: 0 AN: 13896

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12678

East Asian (EAS) AF: 0.00 AC: 0 AN: 29466

South Asian (SAS) AF: 0.00 AC: 0 AN: 26174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3626

European-Non Finnish (NFE) AF: 0.00000498 AC: 2 AN: 401744

Other (OTH) AF: 0.00 AC: 0 AN: 27836

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.88
PhyloP100		-0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2456772; hg19: chr10-62548098;