rs2977490

Positions:

• chr8-140563259-G-A
• chr8-140563259-G-C

Variant summary

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

The NM_012154.5(AGO2):​c.337-625C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,040 control chromosomes in the GnomAD database, including 19,643 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 0.50 (19643 hom., cov: 33)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGO2	NM_012154.5	c.337-625C>T		intron_variant		ENST00000220592.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGO2	ENST00000220592.10	c.337-625C>T		intron_variant		1	NM_012154.5	P1
AGO2	ENST00000519980.5	c.337-625C>T		intron_variant		1
AGO2	ENST00000523609.5	c.144-625C>T		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76495 AN: 151922 Hom.: 19619 Cov.: 33

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.491

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.504 AC: 76569 AN: 152040 Hom.: 19643 Cov.: 33 AF XY: 0.502 AC XY: 37322 AN XY: 74316

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.491

Alfa AF: 0.463 Hom.: 21915

Bravo AF: 0.499

Asia WGS AF: 0.520 AC: 1807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.81

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: rs2977490; hg19: chr8-141573358;