5-55128615-G-C

Position:

chr5-55128615-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001170402.1(CDC20B):c.700C>G(p.Leu234Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000337 in 1,543,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

CDC20B
NM_001170402.1 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.95

Variant links:

Genes affected

CDC20B (HGNC:24222): (cell division cycle 20B) Predicted to enable anaphase-promoting complex binding activity and ubiquitin ligase activator activity. Predicted to be involved in anaphase-promoting complex-dependent catabolic process and positive regulation of anaphase-promoting complex-dependent catabolic process. Predicted to be part of anaphase-promoting complex. [provided by Alliance of Genome Resources, Apr 2022]

CDC20B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3297934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC20B	NM_001170402.1 linkuse as main transcript	c.700C>G	p.Leu234Val	missense_variant, splice_region_variant	7/12	ENST00000381375.7	NP_001163873.1	Q86Y33-1
CDC20B	NM_152623.2 linkuse as main transcript	c.700C>G	p.Leu234Val	missense_variant, splice_region_variant	7/12		NP_689836.2	Q86Y33-2
CDC20B	NM_001145734.2 linkuse as main transcript	c.700C>G	p.Leu234Val	missense_variant, splice_region_variant	7/11		NP_001139206.2	Q86Y33-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDC20B	ENST00000381375.7 linkuse as main transcript	c.700C>G	p.Leu234Val	missense_variant, splice_region_variant	7/12	1	NM_001170402.1	ENSP00000370781.2	Q86Y33-1
CDC20B	ENST00000296733.5 linkuse as main transcript	c.700C>G	p.Leu234Val	missense_variant, splice_region_variant	7/12	1		ENSP00000296733.1	Q86Y33-2
CDC20B	ENST00000322374.10 linkuse as main transcript	c.700C>G	p.Leu234Val	missense_variant, splice_region_variant	7/11	1		ENSP00000315720.6	Q86Y33-3
CDC20B	ENST00000513180.5 linkuse as main transcript	n.700C>G		splice_region_variant, non_coding_transcript_exon_variant	7/12	5		ENSP00000426776.1	Q86Y33-4

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.000368

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000170

AC:

AN:

188014

Hom.:

AF XY:

0.000154

AC XY:

AN XY:

103766

show subpopulations

Gnomad AFR exome

AF:

0.0000749

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000316

Gnomad OTH exome

AF:

0.000247

GnomAD4 exome

AF:

0.000351

AC:

488

AN:

1391028

Hom.:

Cov.:

AF XY:

0.000327

AC XY:

226

AN XY:

690262

show subpopulations

Gnomad4 AFR exome

AF:

0.0000689

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000432

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000429

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000210

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000253

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.700C>G (p.L234V) alteration is located in exon 7 (coding exon 7) of the CDC20B gene. This alteration results from a C to G substitution at nucleotide position 700, causing the leucine (L) at amino acid position 234 to be replaced by a valine (V). 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

0.25

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;T;.

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.3

M;M;M

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.010

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.50

MVP

0.43

MPC

0.78

ClinPred

0.26

GERP RS

4.5

Varity_R

0.26

gMVP

0.20

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over