Genetic Variant ANAPC2:p.Tyr509Tyr (chr9-137180871-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_013366.4(ANAPC2):c.1527C>T(p.Tyr509Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,613,438 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 7 hom., cov: 33)

Exomes 𝑓: 0.00064 ( 14 hom. )

Consequence

ANAPC2
NM_013366.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.413

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 9-137180871-G-A is Benign according to our data. Variant chr9-137180871-G-A is described in ClinVar as [Benign]. Clinvar id is 776484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.413 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00632 (963/152338) while in subpopulation AFR AF= 0.0222 (924/41580). AF 95% confidence interval is 0.021. There are 7 homozygotes in gnomad4. There are 438 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 963 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANAPC2	NM_013366.4 link	c.1527C>T	p.Tyr509Tyr	synonymous_variant	Exon 8 of 13	ENST00000323927.3	NP_037498.1	Q9UJX6-1
ANAPC2	XM_047423274.1 link	c.1527C>T	p.Tyr509Tyr	synonymous_variant	Exon 8 of 13		XP_047279230.1
ANAPC2	XM_047423275.1 link	c.1527C>T	p.Tyr509Tyr	synonymous_variant	Exon 8 of 12		XP_047279231.1
ANAPC2	XM_047423276.1 link	c.1527C>T	p.Tyr509Tyr	synonymous_variant	Exon 8 of 13		XP_047279232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANAPC2	ENST00000323927.3 link	c.1527C>T	p.Tyr509Tyr	synonymous_variant	Exon 8 of 13	1	NM_013366.4	ENSP00000314004.2		Q9UJX6-1

Frequencies

GnomAD3 genomes

AF:

0.00628

AC:

956

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0221

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00156

AC:

392

AN:

250936

Hom.:

AF XY:

0.00115

AC XY:

156

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.0215

Gnomad AMR exome

AF:

0.000839

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000643

AC:

940

AN:

1461100

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

410

AN XY:

726888

show subpopulations

Gnomad4 AFR exome

AF:

0.0234

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.00632

AC:

963

AN:

152338

Hom.:

Cov.:

AF XY:

0.00588

AC XY:

438

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0222

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00287

Hom.:

Bravo

AF:

0.00696

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

5.1

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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