rs2977469

chr8-140539192-A-Gchr8-140539192-A-T

Variant summary

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

The NM_012154.5(AGO2):c.2169+128T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,344,806 control chromosomes in the GnomAD database, including 166,065 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 0.51 (20221 hom., cov: 32)
  • Exomes 𝑓: 0.49 (145844 hom.)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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 = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGO2	NM_012154.5	c.2169+128T>C		intron_variant		ENST00000220592.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGO2	ENST00000220592.10	c.2169+128T>C		intron_variant		1	NM_012154.5	P1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77939 AN: 151906 Hom.: 20176 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.511

GnomAD4 exome AF: 0.491 AC: 585531 AN: 1192782 Hom.: 145844 AF XY: 0.492 AC XY: 289156 AN XY: 587702

Gnomad4 AFR exome AF: 0.556

Gnomad4 AMR exome AF: 0.575

Gnomad4 ASJ exome AF: 0.456

Gnomad4 EAS exome AF: 0.697

Gnomad4 SAS exome AF: 0.552

Gnomad4 FIN exome AF: 0.536

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.496

GnomAD4 genome AF: 0.513 AC: 78044 AN: 152024 Hom.: 20221 Cov.: 32 AF XY: 0.515 AC XY: 38291 AN XY: 74288

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.509

Alfa AF: 0.480 Hom.: 23644

Bravo AF: 0.518

Asia WGS AF: 0.600 AC: 2085 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	0.14
Dann	Benign	0.67

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: rs2977469; hg19: chr8-141549291;