rs2292778

Positions:

• chr8-140558523-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_012154.5(AGO2):​c.840C>T​(p.Arg280=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,613,924 control chromosomes in the GnomAD database, including 251,392 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 0.62 (30639 hom., cov: 34)
  • Exomes 𝑓: 0.55 (220753 hom.)
• Consequence: AGO2 NM_012154.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-2.18 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGO2	NM_012154.5	c.840C>T	p.Arg280=	synonymous_variant	7/19	ENST00000220592.10	NP_036286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10	c.840C>T	p.Arg280=	synonymous_variant	7/19	1	NM_012154.5	ENSP00000220592	P1
AGO2	ENST00000519980.5	c.840C>T	p.Arg280=	synonymous_variant	7/18	1		ENSP00000430176
AGO2	ENST00000523609.5	c.*425C>T		3_prime_UTR_variant, NMD_transcript_variant	6/18	1		ENSP00000430164

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94372 AN: 152054 Hom.: 30591 Cov.: 34

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.587

GnomAD3 exomes AF: 0.581 AC: 145947 AN: 251404 Hom.: 43557 AF XY: 0.573 AC XY: 77805 AN XY: 135866

Gnomad AFR exome AF: 0.837

Gnomad AMR exome AF: 0.671

Gnomad ASJ exome AF: 0.544

Gnomad EAS exome AF: 0.626

Gnomad SAS exome AF: 0.616

Gnomad FIN exome AF: 0.491

Gnomad NFE exome AF: 0.521

Gnomad OTH exome AF: 0.547

GnomAD4 exome AF: 0.546 AC: 798161 AN: 1461752 Hom.: 220753 Cov.: 62 AF XY: 0.546 AC XY: 397044 AN XY: 727176

Gnomad4 AFR exome AF: 0.830

Gnomad4 AMR exome AF: 0.662

Gnomad4 ASJ exome AF: 0.547

Gnomad4 EAS exome AF: 0.587

Gnomad4 SAS exome AF: 0.618

Gnomad4 FIN exome AF: 0.494

Gnomad4 NFE exome AF: 0.527

Gnomad4 OTH exome AF: 0.558

GnomAD4 genome AF: 0.621 AC: 94482 AN: 152172 Hom.: 30639 Cov.: 34 AF XY: 0.620 AC XY: 46115 AN XY: 74390

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.617

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.588

Alfa AF: 0.571 Hom.: 12224

Bravo AF: 0.639

Asia WGS AF: 0.642 AC: 2231 AN: 3478

EpiCase AF: 0.523

EpiControl AF: 0.515

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.21
DANN	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2292778; hg19: chr8-141568622;