8-140551758-C-G

Position:

• chr8-140551758-C-G

Variant summary

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

The NM_012154.5(AGO2):​c.1270-322G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 142,094 control chromosomes in the GnomAD database, including 33,138 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 0.68 (33138 hom., cov: 24)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.46

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGO2	NM_012154.5	c.1270-322G>C		intron_variant		ENST00000220592.10	NP_036286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10	c.1270-322G>C		intron_variant		1	NM_012154.5	ENSP00000220592.5
AGO2	ENST00000519980.5	c.1270-322G>C		intron_variant		1		ENSP00000430176.1
AGO2	ENST00000523609.5	n.*855-322G>C		intron_variant		1		ENSP00000430164.1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 96471 AN: 141980 Hom.: 33073 Cov.: 24

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.626

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.680 AC: 96596 AN: 142094 Hom.: 33138 Cov.: 24 AF XY: 0.683 AC XY: 47075 AN XY: 68878

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.712

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.656

Alfa AF: 0.397 Hom.: 913

Bravo AF: 0.676

Asia WGS AF: 0.680 AC: 2322 AN: 3416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.18

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: rs2977481; hg19: chr8-141561857;