chr9-87969280-C-T

Position:

• chr9-87969280-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039803.3(CDK20):​c.757G>A​(p.Val253Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,820 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (1 hom.)
• Consequence: CDK20 NM_001039803.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2153022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDK20	NM_001039803.3	c.757G>A	p.Val253Met	missense_variant	7/8	ENST00000325303.9	NP_001034892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDK20	ENST00000325303.9	c.757G>A	p.Val253Met	missense_variant	7/8	1	NM_001039803.3	ENSP00000322343.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461820 Hom.: 1 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000809

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2024

The c.757G>A (p.V253M) alteration is located in exon 7 (coding exon 7) of the CDK20 gene. This alteration results from a G to A substitution at nucleotide position 757, causing the valine (V) at amino acid position 253 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	.;.;.;T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.74	T
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.96	N;N;.;N
REVEL	Benign	0.14
Sift	Uncertain	0.0080	D;D;.;D
Sift4G	Uncertain	0.039	D;T;T;D
Polyphen		0.96	.;.;.;D
Vest4		0.34
MutPred		0.51		.;.;.;Gain of disorder (P = 0.0573);
MVP		0.29
MPC		0.20
ClinPred		0.97	D
GERP RS		3.7
Varity_R		0.31
gMVP		0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs1403719210; hg19: chr9-90584195;