8-140625549-G-C

Variant names:

• chr8-140625549-G-C
• rs883596
• NM_012154.5:c.22+9936C>G

Variant summary

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

The NM_012154.5(AGO2):​c.22+9936C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,058 control chromosomes in the GnomAD database, including 7,025 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 0.28 (7025 hom., cov: 32)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435
• Publications: 5 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

LOC107986982 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGO2	NM_012154.5	c.22+9936C>G		intron_variant	Intron 1 of 18	ENST00000220592.10	NP_036286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10	c.22+9936C>G		intron_variant	Intron 1 of 18	1	NM_012154.5	ENSP00000220592.5

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42565 AN: 151940 Hom.: 7006 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.280 AC: 42623 AN: 152058 Hom.: 7025 Cov.: 32 AF XY: 0.280 AC XY: 20808 AN XY: 74332

African (AFR) AF: 0.444 AC: 18410 AN: 41448

American (AMR) AF: 0.357 AC: 5463 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 876 AN: 3472

East Asian (EAS) AF: 0.144 AC: 742 AN: 5170

South Asian (SAS) AF: 0.272 AC: 1311 AN: 4814

European-Finnish (FIN) AF: 0.166 AC: 1759 AN: 10586

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13289 AN: 67970

Other (OTH) AF: 0.260 AC: 548 AN: 2106

Alfa AF: 0.247 Hom.: 688

Bravo AF: 0.299

Asia WGS AF: 0.239 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.59
PhyloP100		0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs883596; hg19: chr8-141635648;