8-140562399-G-A

Position:

• chr8-140562399-G-A

Variant summary

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

The NM_012154.5(AGO2):​c.518+54C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,556,858 control chromosomes in the GnomAD database, including 118,403 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 0.40 (12855 hom., cov: 33)
  • Exomes 𝑓: 0.38 (105548 hom.)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

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 (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGO2	NM_012154.5	c.518+54C>T		intron_variant		ENST00000220592.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGO2	ENST00000220592.10	c.518+54C>T		intron_variant		1	NM_012154.5	P1
AGO2	ENST00000519980.5	c.518+54C>T		intron_variant		1
AGO2	ENST00000523609.5	c.*103+54C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.402 AC: 60988 AN: 151700 Hom.: 12835 Cov.: 33

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.380 AC: 534084 AN: 1405040 Hom.: 105548 AF XY: 0.381 AC XY: 263670 AN XY: 692452

Gnomad4 AFR exome AF: 0.406

Gnomad4 AMR exome AF: 0.624

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.675

Gnomad4 SAS exome AF: 0.467

Gnomad4 FIN exome AF: 0.374

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.386

GnomAD4 genome AF: 0.402 AC: 61056 AN: 151818 Hom.: 12855 Cov.: 33 AF XY: 0.409 AC XY: 30377 AN XY: 74220

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.327

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.359

Alfa AF: 0.366 Hom.: 1254

Bravo AF: 0.414

Asia WGS AF: 0.573 AC: 1987 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	0.21
DANN	Benign	0.69
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: rs2292773; hg19: chr8-141572498;