1-43360761-C-T

Variant summary

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

The NM_001255.3(CDC20):c.877C>T(p.His293Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDC20 NM_001255.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

Genes affected

CDC20 (HGNC:1723): (cell division cycle 20) CDC20 appears to act as a regulatory protein interacting with several other proteins at multiple points in the cell cycle. It is required for two microtubule-dependent processes, nuclear movement prior to anaphase and chromosome separation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC20	NM_001255.3	c.877C>T	p.His293Tyr	missense_variant	8/11	ENST00000310955.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC20	ENST00000310955.11	c.877C>T	p.His293Tyr	missense_variant	8/11	1	NM_001255.3	P1
CDC20	ENST00000372462.1	c.877C>T	p.His293Tyr	missense_variant	7/10	1		P1
CDC20	ENST00000478882.1	n.652C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Oct 03, 2022

The c.877C>T (p.H293Y) alteration is located in exon 8 (coding exon 7) of the CDC20 gene. This alteration results from a C to T substitution at nucleotide position 877, causing the histidine (H) at amino acid position 293 to be replaced by a tyrosine (Y). 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	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.51	P;P
Vest4		0.78
MutPred		0.57		Gain of sheet (P = 0.0049);Gain of sheet (P = 0.0049);
MVP		0.71
MPC		0.54
ClinPred		0.88	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.91
gMVP		0.49

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-43826432;