Variant 8-140539313-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012154.5(AGO2):c.2169+7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,598,072 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 29 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 23 hom. )

Consequence

AGO2
NM_012154.5 splice_region, intron

Scores

Splicing: ADA: 0.00001847

Clinical Significance

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

Conservation

PhyloP100: -0.892

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 8-140539313-A-G is Benign according to our data. Variant chr8-140539313-A-G is described in ClinVar as [Benign]. Clinvar id is 786125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1616/152100) while in subpopulation AFR AF= 0.0368 (1527/41480). AF 95% confidence interval is 0.0353. There are 29 homozygotes in gnomad4. There are 742 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1616 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGO2	NM_012154.5 linkuse as main transcript	c.2169+7T>C		splice_region_variant, intron_variant		ENST00000220592.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGO2	ENST00000220592.10 linkuse as main transcript	c.2169+7T>C		splice_region_variant, intron_variant		1	NM_012154.5	P1	Q9UKV8-1

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1614

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0369

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00277

AC:

671

AN:

241914

Hom.:

AF XY:

0.00197

AC XY:

257

AN XY:

130584

show subpopulations

Gnomad AFR exome

AF:

0.0360

Gnomad AMR exome

AF:

0.00212

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000688

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000914

Gnomad OTH exome

AF:

0.00119

GnomAD4 exome

AF:

0.00103

AC:

1483

AN:

1445972

Hom.:

Cov.:

AF XY:

0.000905

AC XY:

649

AN XY:

717438

show subpopulations

Gnomad4 AFR exome

AF:

0.0359

Gnomad4 AMR exome

AF:

0.00234

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000591

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000399

Gnomad4 OTH exome

AF:

0.00231

GnomAD4 genome

AF:

0.0106

AC:

1616

AN:

152100

Hom.:

Cov.:

AF XY:

0.00998

AC XY:

742

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0368

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00485

Hom.:

Bravo

AF:

0.0119

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.34

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.0

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