Variant 8-140551294-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012154.5(AGO2):c.1403+9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,513,356 control chromosomes in the GnomAD database, including 237,217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 32111 hom., cov: 33)

Exomes 𝑓: 0.54 ( 205106 hom. )

Consequence

AGO2
NM_012154.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.78

Variant links:

Genes affected

AGO2 (HGNC:3263): (argonaute RISC catalytic component 2) This gene encodes a member of the Argonaute family of proteins which play a role in RNA interference. The encoded protein is highly basic, and contains a PAZ domain and a PIWI domain. It may interact with dicer1 and play a role in short-interfering-RNA-mediated gene silencing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

AGO2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 8-140551294-G-C is Benign according to our data. Variant chr8-140551294-G-C is described in ClinVar as [Benign]. Clinvar id is 768267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGO2	NM_012154.5 linkuse as main transcript	c.1403+9C>G		intron_variant		ENST00000220592.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
AGO2	ENST00000220592.10 linkuse as main transcript	c.1403+9C>G	intron_variant	1	NM_012154.5	P1	Q9UKV8-1
AGO2	ENST00000519980.5 linkuse as main transcript	c.1403+9C>G	intron_variant	1			Q9UKV8-2
AGO2	ENST00000523609.5 linkuse as main transcript	c.*988+9C>G	intron_variant, NMD_transcript_variant	1

Frequencies

GnomAD3 genomes

AF:

0.632

AC:

96113

AN:

151980

Hom.:

32056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.862

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.632

Gnomad ASJ

AF:

0.548

Gnomad EAS

AF:

0.623

Gnomad SAS

AF:

0.620

Gnomad FIN

AF:

0.494

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.525

Gnomad OTH

AF:

0.595

GnomAD3 exomes

AF:

0.574

AC:

117904

AN:

205340

Hom.:

35201

AF XY:

0.565

AC XY:

62952

AN XY:

111340

show subpopulations

Gnomad AFR exome

AF:

0.875

Gnomad AMR exome

AF:

0.667

Gnomad ASJ exome

AF:

0.526

Gnomad EAS exome

AF:

0.627

Gnomad SAS exome

AF:

0.607

Gnomad FIN exome

AF:

0.485

Gnomad NFE exome

AF:

0.514

Gnomad OTH exome

AF:

0.539

GnomAD4 exome

AF:

0.545

AC:

741325

AN:

1361258

Hom.:

205106

Cov.:

AF XY:

0.544

AC XY:

365284

AN XY:

671184

show subpopulations

Gnomad4 AFR exome

AF:

0.871

Gnomad4 AMR exome

AF:

0.656

Gnomad4 ASJ exome

AF:

0.538

Gnomad4 EAS exome

AF:

0.585

Gnomad4 SAS exome

AF:

0.616

Gnomad4 FIN exome

AF:

0.491

Gnomad4 NFE exome

AF:

0.527

Gnomad4 OTH exome

AF:

0.560

GnomAD4 genome

AF:

0.633

AC:

96230

AN:

152098

Hom.:

32111

Cov.:

AF XY:

0.631

AC XY:

46944

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.861

Gnomad4 AMR

AF:

0.633

Gnomad4 ASJ

AF:

0.548

Gnomad4 EAS

AF:

0.623

Gnomad4 SAS

AF:

0.620

Gnomad4 FIN

AF:

0.494

Gnomad4 NFE

AF:

0.525

Gnomad4 OTH

AF:

0.594

Alfa

AF:

0.463

Hom.:

2257

Bravo

AF:

0.652

Asia WGS

AF:

0.652

AC:

2265

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	GeneDx	Aug 12, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

AGO2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 04, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.024

DANN

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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