10-60792132-A-T

Variant names:

• chr10-60792132-A-T
• rs2456778
• NM_001786.5:c.654-16A>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.654-16A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 1,597,164 control chromosomes in the GnomAD database, including 477,806 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.78 (45901 hom., cov: 32)
  • Exomes 𝑓: 0.77 (431905 hom.)
• Consequence: CDK1 NM_001786.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491
• Publications: 12 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: This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_addAF=-0.866202).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDK1	NM_001786.5	c.654-16A>T		intron_variant	Intron 6 of 7	ENST00000395284.8	NP_001777.1
CDK1	NM_001320918.1	c.654-16A>T		intron_variant	Intron 6 of 7		NP_001307847.1
CDK1	NM_033379.5	c.483-16A>T		intron_variant	Intron 5 of 6		NP_203698.1
CDK1	XM_005270303.4	c.654-16A>T		intron_variant	Intron 6 of 7		XP_005270360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDK1	ENST00000395284.8	c.654-16A>T		intron_variant	Intron 6 of 7	1	NM_001786.5	ENSP00000378699.3

Frequencies

GnomAD3 genomes AF: 0.777 AC: 117754 AN: 151514 Hom.: 45863 Cov.: 32

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.774

GnomAD2 exomes AF: 0.794 AC: 187930 AN: 236656 AF XY: 0.794

Gnomad AFR exome AF: 0.757

Gnomad AMR exome AF: 0.797

Gnomad ASJ exome AF: 0.787

Gnomad EAS exome AF: 0.856

Gnomad FIN exome AF: 0.860

Gnomad NFE exome AF: 0.774

Gnomad OTH exome AF: 0.782

GnomAD4 exome AF: 0.772 AC: 1116496 AN: 1445534 Hom.: 431905 Cov.: 33 AF XY: 0.773 AC XY: 555387 AN XY: 718618

African (AFR) AF: 0.758 AC: 24444 AN: 32228

American (AMR) AF: 0.800 AC: 32788 AN: 40964

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 20007 AN: 25310

East Asian (EAS) AF: 0.813 AC: 32193 AN: 39586

South Asian (SAS) AF: 0.804 AC: 67001 AN: 83330

European-Finnish (FIN) AF: 0.860 AC: 45562 AN: 52962

Middle Eastern (MID) AF: 0.784 AC: 4426 AN: 5646

European-Non Finnish (NFE) AF: 0.763 AC: 843342 AN: 1105962

Other (OTH) AF: 0.785 AC: 46733 AN: 59546

GnomAD4 genome AF: 0.777 AC: 117848 AN: 151630 Hom.: 45901 Cov.: 32 AF XY: 0.782 AC XY: 57957 AN XY: 74074

African (AFR) AF: 0.757 AC: 31282 AN: 41306

American (AMR) AF: 0.790 AC: 12039 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2715 AN: 3468

East Asian (EAS) AF: 0.839 AC: 4332 AN: 5166

South Asian (SAS) AF: 0.802 AC: 3866 AN: 4818

European-Finnish (FIN) AF: 0.867 AC: 9130 AN: 10530

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 51924 AN: 67800

Other (OTH) AF: 0.771 AC: 1615 AN: 2094

Alfa AF: 0.770 Hom.: 8183

Bravo AF: 0.772

TwinsUK AF: 0.756 AC: 2805

ALSPAC AF: 0.753 AC: 2902

ESP6500AA AF: 0.761 AC: 3347

ESP6500EA AF: 0.759 AC: 6518

ExAC AF: 0.790 AC: 95780

Asia WGS AF: 0.786 AC: 2732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.26
FATHMM_MKL	Benign	0.099	N
PhyloP100		-0.49
GERP RS		1.1
BranchPoint Hunter		4.0
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: rs2456778; hg19: chr10-62551890; COSMIC: COSV57349951; COSMIC: COSV57349951;