rs4961226

chr8-140632456-T-G

Variant summary

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

The NM_012154.5(AGO2):c.22+3029A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,270 control chromosomes in the GnomAD database, including 61,603 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 0.90 (61603 hom., cov: 33)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGO2	NM_012154.5	c.22+3029A>C		intron_variant		ENST00000220592.10
AGO2	NM_001164623.3	c.22+3029A>C		intron_variant
AGO2	XM_011516968.3	c.-117+9737A>C		intron_variant
AGO2	XM_047421697.1	c.-235+3029A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGO2	ENST00000220592.10	c.22+3029A>C		intron_variant		1	NM_012154.5	P1

Frequencies

GnomAD3 genomes AF: 0.896 AC: 136385 AN: 152152 Hom.: 61537 Cov.: 33

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.906

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

GnomAD4 genome AF: 0.897 AC: 136511 AN: 152270 Hom.: 61603 Cov.: 33 AF XY: 0.893 AC XY: 66465 AN XY: 74448

Gnomad4 AFR AF: 0.975

Gnomad4 AMR AF: 0.924

Gnomad4 ASJ AF: 0.941

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.837

Gnomad4 NFE AF: 0.874

Gnomad4 OTH AF: 0.907

Alfa AF: 0.890 Hom.: 15466

Bravo AF: 0.906

Asia WGS AF: 0.749 AC: 2606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.7
Dann	Benign	0.48

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: rs4961226; hg19: chr8-141642555;