8-140581794-C-G

Position:

• chr8-140581794-C-G

Variant summary

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

The NM_012154.5(AGO2):​c.215+3325G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,206 control chromosomes in the GnomAD database, including 1,770 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 0.13 (1770 hom., cov: 33)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGO2	NM_012154.5	c.215+3325G>C		intron_variant		ENST00000220592.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGO2	ENST00000220592.10	c.215+3325G>C		intron_variant		1	NM_012154.5	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20198 AN: 152086 Hom.: 1769 Cov.: 33

Gnomad AFR AF: 0.0315

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.133 AC: 20202 AN: 152206 Hom.: 1770 Cov.: 33 AF XY: 0.138 AC XY: 10246 AN XY: 74412

Gnomad4 AFR AF: 0.0314

Gnomad4 AMR AF: 0.0997

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.149

Alfa AF: 0.160 Hom.: 299

Bravo AF: 0.120

Asia WGS AF: 0.208 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.6
DANN	Benign	0.44

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: rs11776034; hg19: chr8-141591893;