rs10088596

Positions:

• chr8-140630195-T-C

Variant summary

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

The NM_012154.5(AGO2):​c.22+5290A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 152,142 control chromosomes in the GnomAD database, including 36,652 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 0.69 (36652 hom., cov: 33)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.457

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGO2	NM_012154.5	c.22+5290A>G		intron_variant		ENST00000220592.10	NP_036286.2
AGO2	NM_001164623.3	c.22+5290A>G		intron_variant			NP_001158095.1
AGO2	XM_011516968.3	c.-117+11998A>G		intron_variant			XP_011515270.3
AGO2	XM_047421697.1	c.-235+5290A>G		intron_variant			XP_047277653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10	c.22+5290A>G		intron_variant		1	NM_012154.5	ENSP00000220592	P1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104964 AN: 152024 Hom.: 36620 Cov.: 33

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.690 AC: 105048 AN: 152142 Hom.: 36652 Cov.: 33 AF XY: 0.691 AC XY: 51364 AN XY: 74368

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.685

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.715

Alfa AF: 0.711 Hom.: 17569

Bravo AF: 0.695

Asia WGS AF: 0.592 AC: 2062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs10088596; hg19: chr8-141640294;