Variant 2-111856852-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 8P and 8B. PVS1BP6_Very_Strong

The NM_022662.4(ANAPC1):c.1393C>T(p.Gln465Ter) variant causes a stop gained change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.082 ( 0 hom., cov: 33)

Exomes 𝑓: 0.28 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ANAPC1
NM_022662.4 stop_gained

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.60

Variant links:

Genes affected

ANAPC1 (HGNC:19988): (anaphase promoting complex subunit 1) This gene encodes a subunit of the anaphase-promoting complex. This complex is an E3 ubiquitin ligase that regulates progression through the metaphase to anaphase portion of the cell cycle by ubiquitinating proteins which targets them for degradation. [provided by RefSeq, Dec 2011]

ANAPC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

BP6

Variant 2-111856852-G-A is Benign according to our data. Variant chr2-111856852-G-A is described in ClinVar as [Benign]. Clinvar id is 402367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANAPC1	NM_022662.4 linkuse as main transcript	c.1393C>T	p.Gln465Ter	stop_gained	12/48	ENST00000341068.8	NP_073153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ANAPC1	ENST00000341068.8 linkuse as main transcript	c.1393C>T	p.Gln465Ter	stop_gained	12/48	1	NM_022662.4	ENSP00000339109	P1
ANAPC1	ENST00000482177.1 linkuse as main transcript	n.214C>T		non_coding_transcript_exon_variant	1/2	2
ANAPC1	ENST00000427997.5 linkuse as main transcript			upstream_gene_variant		1		ENSP00000396695

Frequencies

GnomAD3 genomes

AF:

0.0816

AC:

6366

AN:

78002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0600

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.0924

Gnomad ASJ

AF:

0.0697

Gnomad EAS

AF:

0.0943

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0811

Gnomad OTH

AF:

0.132

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.282

AC:

272953

AN:

967794

Hom.:

Cov.:

AF XY:

0.277

AC XY:

134170

AN XY:

484398

show subpopulations

Gnomad4 AFR exome

AF:

0.211

Gnomad4 AMR exome

AF:

0.210

Gnomad4 ASJ exome

AF:

0.191

Gnomad4 EAS exome

AF:

0.0898

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.190

Gnomad4 NFE exome

AF:

0.311

Gnomad4 OTH exome

AF:

0.238

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0816

AC:

6368

AN:

78084

Hom.:

Cov.:

AF XY:

0.0849

AC XY:

3287

AN XY:

38726

show subpopulations

Gnomad4 AFR

AF:

0.0601

Gnomad4 AMR

AF:

0.0922

Gnomad4 ASJ

AF:

0.0697

Gnomad4 EAS

AF:

0.0944

Gnomad4 SAS

AF:

0.115

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.0811

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.213

Hom.:

ExAC

AF:

0.430

AC:

52254

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.61

BayesDel_noAF

Pathogenic

0.63

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Uncertain

0.94

MutationTaster

Benign

1.0e-37

Vest4

0.92

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.24

Position offset: 34

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