chr8-140562068-C-T

Variant names:

• chr8-140562068-C-T
• rs3928672
• NM_012154.5:c.518+385G>A

Variant summary

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

The NM_012154.5(AGO2):​c.518+385G>A 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 152,158 control chromosomes in the GnomAD database, including 3,423 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 (3423 hom., cov: 33)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGO2	NM_012154.5	c.518+385G>A		intron_variant	Intron 4 of 18	ENST00000220592.10	NP_036286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10	c.518+385G>A		intron_variant	Intron 4 of 18	1	NM_012154.5	ENSP00000220592.5
AGO2	ENST00000519980.5	c.518+385G>A		intron_variant	Intron 4 of 17	1		ENSP00000430176.1
AGO2	ENST00000523609.5	n.*103+385G>A		intron_variant	Intron 3 of 17	1		ENSP00000430164.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31009 AN: 152040 Hom.: 3424 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.204 AC: 31018 AN: 152158 Hom.: 3423 Cov.: 33 AF XY: 0.209 AC XY: 15565 AN XY: 74386

African (AFR) AF: 0.119 AC: 4935 AN: 41536

American (AMR) AF: 0.155 AC: 2366 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 746 AN: 3470

East Asian (EAS) AF: 0.283 AC: 1461 AN: 5166

South Asian (SAS) AF: 0.235 AC: 1134 AN: 4826

European-Finnish (FIN) AF: 0.306 AC: 3231 AN: 10556

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16358 AN: 67996

Other (OTH) AF: 0.228 AC: 480 AN: 2106

Alfa AF: 0.221 Hom.: 7413

Bravo AF: 0.189

Asia WGS AF: 0.240 AC: 837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.035
DANN	Benign	0.72
PhyloP100		-1.1
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: rs3928672; hg19: chr8-141572167;