rs2271735

Variant names:

• chr8-140559211-C-A
• rs2271735
• NM_012154.5:c.790+184G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012154.5(AGO2):​c.790+184G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,014 control chromosomes in the GnomAD database, including 3,888 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 0.20 (3888 hom., cov: 33)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 6 publications found

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]

AGO2 Gene-Disease associations (from GenCC):

• Lessel-Kreienkamp syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGO2	NM_012154.5	c.790+184G>T		intron_variant	Intron 6 of 18	ENST00000220592.10	NP_036286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10	c.790+184G>T		intron_variant	Intron 6 of 18	1	NM_012154.5	ENSP00000220592.5
AGO2	ENST00000519980.5	c.790+184G>T		intron_variant	Intron 6 of 17	1		ENSP00000430176.1
AGO2	ENST00000523609.5	n.*375+184G>T		intron_variant	Intron 5 of 17	1		ENSP00000430164.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31005 AN: 151896 Hom.: 3888 Cov.: 33

Gnomad AFR AF: 0.0628

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.204 AC: 31004 AN: 152014 Hom.: 3888 Cov.: 33 AF XY: 0.207 AC XY: 15375 AN XY: 74280

African (AFR) AF: 0.0627 AC: 2600 AN: 41492

American (AMR) AF: 0.156 AC: 2386 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 771 AN: 3470

East Asian (EAS) AF: 0.279 AC: 1438 AN: 5160

South Asian (SAS) AF: 0.232 AC: 1114 AN: 4810

European-Finnish (FIN) AF: 0.338 AC: 3561 AN: 10548

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18275 AN: 67942

Other (OTH) AF: 0.218 AC: 459 AN: 2108

Alfa AF: 0.247 Hom.: 3592

Bravo AF: 0.184

Asia WGS AF: 0.236 AC: 821 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	0.20
DANN	Benign	0.39
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2271735; hg19: chr8-141569310;