rs753328488

Variant names:

• chr9-87967484-C-T
• rs753328488
• NM_001039803.3:c.1019G>A

Variant summary

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

The NM_001039803.3(CDK20):​c.1019G>A​(p.Arg340Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,555,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: CDK20 NM_001039803.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.272
• Publications: 0 publications found

Genes affected

CDK20 (HGNC:21420): (cyclin dependent kinase 20) The protein encoded by this gene contains a kinase domain most closely related to the cyclin-dependent protein kinases. The encoded kinase may activate cyclin-dependent kinase 2 and is involved in cell growth. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Dec 2009]

CDK20 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000303948 (HGNC:):

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 (MetaRNN=0.066171676).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039803.3. 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
	CDK20	NM_001039803.3	MANE Select	c.1019G>A	p.Arg340Gln	missense	Exon 8 of 8	NP_001034892.1	Q8IZL9-1
	CDK20	NM_178432.4		c.995G>A	p.Arg332Gln	missense	Exon 7 of 7	NP_848519.1	Q8IZL9-4
	CDK20	NM_012119.5		c.956G>A	p.Arg319Gln	missense	Exon 7 of 7	NP_036251.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDK20	ENST00000325303.9	TSL:1 MANE Select	c.1019G>A	p.Arg340Gln	missense	Exon 8 of 8	ENSP00000322343.8	Q8IZL9-1
	CDK20	ENST00000375883.7	TSL:1	c.956G>A	p.Arg319Gln	missense	Exon 7 of 7	ENSP00000365043.3	Q8IZL9-5
	CDK20	ENST00000605159.5	TSL:1	c.*100G>A		3_prime_UTR	Exon 7 of 7	ENSP00000474485.1	Q8IZL9-3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152038 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000307 AC: 5 AN: 162754 AF XY: 0.0000467

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000793

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000310

Gnomad OTH exome AF: 0.000220

GnomAD4 exome AF: 0.0000135 AC: 19 AN: 1402974 Hom.: 0 Cov.: 31 AF XY: 0.0000173 AC XY: 12 AN XY: 692302

African (AFR) AF: 0.00 AC: 0 AN: 31748

American (AMR) AF: 0.000111 AC: 4 AN: 36096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25202

East Asian (EAS) AF: 0.0000279 AC: 1 AN: 35886

South Asian (SAS) AF: 0.00 AC: 0 AN: 79376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.0000111 AC: 12 AN: 1081160

Other (OTH) AF: 0.0000343 AC: 2 AN: 58228

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152038 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74262

African (AFR) AF: 0.00 AC: 0 AN: 41370

American (AMR) AF: 0.0000655 AC: 1 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000264

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	0.070
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.27
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.34	N
REVEL	Benign	0.070
Sift	Benign	0.28	T
Sift4G	Benign	0.46	T
Polyphen		0.012	B
Vest4		0.17
MVP		0.32
MPC		0.035
ClinPred		0.048	T
GERP RS		3.8
Varity_R		0.041
gMVP		0.20
Mutation Taster		=92/8	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: rs753328488; hg19: chr9-90582399; COSMIC: COSV99050885; COSMIC: COSV99050885;