Variant 5-55114222-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001170402.1(CDC20B):c.1556A>G(p.Tyr519Cys) 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 1,461,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CDC20B
NM_001170402.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.439

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06830755).

BP6

Variant 5-55114222-T-C is Benign according to our data. Variant chr5-55114222-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2530240.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDC20B	NM_001170402.1 linkuse as main transcript	c.1556A>G	p.Tyr519Cys	missense_variant	12/12	ENST00000381375.7	NP_001163873.1	Q86Y33-1
CDC20B	NM_152623.2 linkuse as main transcript	c.1544A>G	p.Tyr515Cys	missense_variant	12/12		NP_689836.2	Q86Y33-2
CDC20B	NM_001145734.2 linkuse as main transcript	c.1430A>G	p.Tyr477Cys	missense_variant	11/11		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.1556A>G	p.Tyr519Cys	missense_variant	12/12	1	NM_001170402.1	ENSP00000370781.2	Q86Y33-1
CDC20B	ENST00000296733.5 linkuse as main transcript	c.1544A>G	p.Tyr515Cys	missense_variant	12/12	1		ENSP00000296733.1	Q86Y33-2
CDC20B	ENST00000322374.10 linkuse as main transcript	c.1430A>G	p.Tyr477Cys	missense_variant	11/11	1		ENSP00000315720.6	Q86Y33-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461182

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726892

show subpopulations

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:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 27, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.079

.;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00069

LIST_S2

Benign

0.61

T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.068

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

.;L;.

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Benign

0.059

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.0

B;B;B

Vest4

0.076

MutPred

0.65

.;Loss of disorder (P = 0.0604);.;

MVP

0.12

MPC

0.63

ClinPred

0.19

GERP RS

-2.3

Varity_R

0.15

gMVP

0.34

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over