Variant 8-140541308-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_012154.5(AGO2):c.1890C>T(p.Arg630=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,612,310 control chromosomes in the GnomAD database, including 55,485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 4276 hom., cov: 33)

Exomes 𝑓: 0.26 ( 51209 hom. )

Consequence

AGO2
NM_012154.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.89

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 8-140541308-G-A is Benign according to our data. Variant chr8-140541308-G-A is described in ClinVar as [Benign]. Clinvar id is 1183693.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.89 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 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.1890C>T	p.Arg630=	synonymous_variant	15/19	ENST00000220592.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGO2	ENST00000220592.10 linkuse as main transcript	c.1890C>T	p.Arg630=	synonymous_variant	15/19	1	NM_012154.5	P1	Q9UKV8-1
AGO2	ENST00000519980.5 linkuse as main transcript	c.1890C>T	p.Arg630=	synonymous_variant	15/18	1			Q9UKV8-2
AGO2	ENST00000523609.5 linkuse as main transcript	c.*1475C>T		3_prime_UTR_variant, NMD_transcript_variant	14/18	1
AGO2	ENST00000520412.1 linkuse as main transcript	n.150C>T		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33277

AN:

152142

Hom.:

4273

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0881

Gnomad AMI

AF:

0.340

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.242

GnomAD3 exomes

AF:

0.255

AC:

63157

AN:

247394

Hom.:

8434

AF XY:

0.258

AC XY:

34637

AN XY:

134016

show subpopulations

Gnomad AFR exome

AF:

0.0795

Gnomad AMR exome

AF:

0.221

Gnomad ASJ exome

AF:

0.257

Gnomad EAS exome

AF:

0.332

Gnomad SAS exome

AF:

0.240

Gnomad FIN exome

AF:

0.319

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.262

GnomAD4 exome

AF:

0.261

AC:

381394

AN:

1460050

Hom.:

51209

Cov.:

AF XY:

0.261

AC XY:

189767

AN XY:

726276

show subpopulations

Gnomad4 AFR exome

AF:

0.0849

Gnomad4 AMR exome

AF:

0.226

Gnomad4 ASJ exome

AF:

0.259

Gnomad4 EAS exome

AF:

0.376

Gnomad4 SAS exome

AF:

0.238

Gnomad4 FIN exome

AF:

0.316

Gnomad4 NFE exome

AF:

0.263

Gnomad4 OTH exome

AF:

0.258

GnomAD4 genome

AF:

0.219

AC:

33295

AN:

152260

Hom.:

4276

Cov.:

AF XY:

0.221

AC XY:

16462

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0884

Gnomad4 AMR

AF:

0.218

Gnomad4 ASJ

AF:

0.247

Gnomad4 EAS

AF:

0.340

Gnomad4 SAS

AF:

0.237

Gnomad4 FIN

AF:

0.308

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.245

Alfa

AF:

0.256

Hom.:

9174

Bravo

AF:

0.207

Asia WGS

AF:

0.273

AC:

950

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 02, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

Cadd

Benign

5.7

Dann

Benign

0.77

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