Variant 9-137175736-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000323927.3(ANAPC2):c.1992G>A(p.Ala664Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,612,072 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0028 ( 13 hom. )

Consequence

ANAPC2
ENST00000323927.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.63

Variant links:

Genes affected

ANAPC2 (HGNC:19989): (anaphase promoting complex subunit 2) A large protein complex, termed the anaphase-promoting complex (APC), or the cyclosome, promotes metaphase-anaphase transition by ubiquitinating its specific substrates such as mitotic cyclins and anaphase inhibitor, which are subsequently degraded by the 26S proteasome. Biochemical studies have shown that the vertebrate APC contains eight subunits. The composition of the APC is highly conserved in organisms from yeast to humans. The product of this gene is a component of the complex and shares sequence similarity with a recently identified family of proteins called cullins, which may also be involved in ubiquitin-mediated degradation. [provided by RefSeq, Jul 2008]

ANAPC2 links:

ANAPC2 (HGNC:):

ANAPC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 9-137175736-C-T is Benign according to our data. Variant chr9-137175736-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 787588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.63 with no splicing effect.

BS2

High AC in GnomAd4 at 362 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANAPC2	NM_013366.4 linkuse as main transcript	c.1992G>A	p.Ala664Ala	synonymous_variant	11/13	ENST00000323927.3	NP_037498.1	Q9UJX6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANAPC2	ENST00000323927.3 linkuse as main transcript	c.1992G>A	p.Ala664Ala	synonymous_variant	11/13	1	NM_013366.4	ENSP00000314004.2		Q9UJX6-1

Frequencies

GnomAD3 genomes

AF:

0.00236

AC:

359

AN:

152272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00272

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00281

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00177

AC:

437

AN:

246496

Hom.:

AF XY:

0.00180

AC XY:

241

AN XY:

134152

show subpopulations

Gnomad AFR exome

AF:

0.00222

Gnomad AMR exome

AF:

0.00180

Gnomad ASJ exome

AF:

0.000504

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000526

Gnomad FIN exome

AF:

0.000143

Gnomad NFE exome

AF:

0.00270

Gnomad OTH exome

AF:

0.00283

GnomAD4 exome

AF:

0.00279

AC:

4079

AN:

1459682

Hom.:

Cov.:

AF XY:

0.00271

AC XY:

1969

AN XY:

726126

show subpopulations

Gnomad4 AFR exome

AF:

0.00242

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.000613

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000650

Gnomad4 FIN exome

AF:

0.000231

Gnomad4 NFE exome

AF:

0.00326

Gnomad4 OTH exome

AF:

0.00322

GnomAD4 genome

AF:

0.00238

AC:

362

AN:

152390

Hom.:

Cov.:

AF XY:

0.00225

AC XY:

168

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.00279

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.000470

Gnomad4 NFE

AF:

0.00281

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00323

Hom.:

Bravo

AF:

0.00276

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00311

EpiControl

AF:

0.00291

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2022	ANAPC2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.089

DANN

Benign

0.89

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