rs2292780

Positions:

• chr8-140551258-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012154.5(AGO2):​c.1403+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 1,448,854 control chromosomes in the GnomAD database, including 3,043 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.077 (572 hom., cov: 33)
  • Exomes 𝑓: 0.060 (2471 hom.)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGO2	NM_012154.5	c.1403+45G>A		intron_variant		ENST00000220592.10	NP_036286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10	c.1403+45G>A		intron_variant		1	NM_012154.5	ENSP00000220592	P1
AGO2	ENST00000519980.5	c.1403+45G>A		intron_variant		1		ENSP00000430176
AGO2	ENST00000523609.5	c.*988+45G>A		intron_variant, NMD_transcript_variant		1		ENSP00000430164

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11682 AN: 152160 Hom.: 569 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0815

Gnomad AMR AF: 0.0519

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.0409

Gnomad SAS AF: 0.0449

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0586

Gnomad OTH AF: 0.0692

GnomAD3 exomes AF: 0.0595 AC: 9501 AN: 159692 Hom.: 347 AF XY: 0.0587 AC XY: 5047 AN XY: 86004

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.0438

Gnomad ASJ exome AF: 0.0664

Gnomad EAS exome AF: 0.0411

Gnomad SAS exome AF: 0.0520

Gnomad FIN exome AF: 0.0381

Gnomad NFE exome AF: 0.0599

Gnomad OTH exome AF: 0.0583

GnomAD4 exome AF: 0.0596 AC: 77239 AN: 1296576 Hom.: 2471 Cov.: 29 AF XY: 0.0594 AC XY: 37668 AN XY: 634430

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.0458

Gnomad4 ASJ exome AF: 0.0713

Gnomad4 EAS exome AF: 0.0514

Gnomad4 SAS exome AF: 0.0490

Gnomad4 FIN exome AF: 0.0403

Gnomad4 NFE exome AF: 0.0594

Gnomad4 OTH exome AF: 0.0621

GnomAD4 genome AF: 0.0768 AC: 11689 AN: 152278 Hom.: 572 Cov.: 33 AF XY: 0.0746 AC XY: 5557 AN XY: 74462

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0518

Gnomad4 ASJ AF: 0.0704

Gnomad4 EAS AF: 0.0410

Gnomad4 SAS AF: 0.0449

Gnomad4 FIN AF: 0.0419

Gnomad4 NFE AF: 0.0586

Gnomad4 OTH AF: 0.0685

Alfa AF: 0.0592 Hom.: 422

Bravo AF: 0.0810

Asia WGS AF: 0.0530 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs2292780; hg19: chr8-141561357; COSMIC: COSV55044928; COSMIC: COSV55044928;