rs7016981

Positions:

• chr8-140603795-T-C

Variant summary

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

The ENST00000220592.10(AGO2):​c.23-18484A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,146 control chromosomes in the GnomAD database, including 9,861 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 0.35 (9861 hom., cov: 33)
• Consequence: AGO2 ENST00000220592.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGO2	NM_012154.5	c.23-18484A>G		intron_variant		ENST00000220592.10	NP_036286.2
AGO2	NM_001164623.3	c.23-18484A>G		intron_variant			NP_001158095.1
AGO2	XM_011516968.3	c.-116-18484A>G		intron_variant			XP_011515270.3
AGO2	XM_047421697.1	c.-117+2002A>G		intron_variant			XP_047277653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10	c.23-18484A>G		intron_variant		1	NM_012154.5	ENSP00000220592	P1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53081 AN: 152028 Hom.: 9842 Cov.: 33

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.349 AC: 53147 AN: 152146 Hom.: 9861 Cov.: 33 AF XY: 0.348 AC XY: 25863 AN XY: 74376

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.334

Alfa AF: 0.324 Hom.: 1680

Bravo AF: 0.360

Asia WGS AF: 0.252 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.6
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7016981; hg19: chr8-141613894;