chr9-87967468-C-T

Variant names:

• chr9-87967468-C-T
• rs200903388
• NM_001039803.3:c.1035G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The NM_001039803.3(CDK20):​c.1035G>A​(p.Glu345Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000643 in 1,554,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: CDK20 NM_001039803.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.122
• 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 (REVEL=0.021).
• BP6: Variant 9-87967468-C-T is Benign according to our data. Variant chr9-87967468-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3051912.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.122 with no splicing effect.

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.1035G>A	p.Glu345Glu	synonymous	Exon 8 of 8	NP_001034892.1	Q8IZL9-1
	CDK20	NM_178432.4		c.1011G>A	p.Glu337Glu	synonymous	Exon 7 of 7	NP_848519.1	Q8IZL9-4
	CDK20	NM_012119.5		c.972G>A	p.Glu324Glu	synonymous	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.1035G>A	p.Glu345Glu	synonymous	Exon 8 of 8	ENSP00000322343.8	Q8IZL9-1
	CDK20	ENST00000375883.7	TSL:1	c.972G>A	p.Glu324Glu	synonymous	Exon 7 of 7	ENSP00000365043.3	Q8IZL9-5
	CDK20	ENST00000605159.5	TSL:1	c.*116G>A		3_prime_UTR	Exon 7 of 7	ENSP00000474485.1	Q8IZL9-3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

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: 0.00 AC: 0 AN: 161546 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000571 AC: 8 AN: 1401786 Hom.: 0 Cov.: 31 AF XY: 0.00000578 AC XY: 4 AN XY: 691600

African (AFR) AF: 0.00 AC: 0 AN: 31694

American (AMR) AF: 0.00 AC: 0 AN: 35934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25196

East Asian (EAS) AF: 0.00 AC: 0 AN: 35846

South Asian (SAS) AF: 0.00 AC: 0 AN: 79326

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080422

Other (OTH) AF: 0.000138 AC: 8 AN: 58164

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152298 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74466

African (AFR) AF: 0.00 AC: 0 AN: 41562

American (AMR) AF: 0.00 AC: 0 AN: 15302

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

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CDK20-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.4
DANN	Benign	0.34
PhyloP100		-0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200903388; hg19: chr9-90582383;