rs7824304

chr8-140573918-C-T

Variant summary

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

The NM_012154.5(AGO2):c.216-986G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,104 control chromosomes in the GnomAD database, including 6,462 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 0.29 (6462 hom., cov: 32)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGO2	NM_012154.5	c.216-986G>A		intron_variant		ENST00000220592.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGO2	ENST00000220592.10	c.216-986G>A		intron_variant		1	NM_012154.5	P1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43543 AN: 151986 Hom.: 6457 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.0408

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.286 AC: 43557 AN: 152104 Hom.: 6462 Cov.: 32 AF XY: 0.280 AC XY: 20838 AN XY: 74354

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.0409

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.306

Alfa AF: 0.324 Hom.: 10781

Bravo AF: 0.285

Asia WGS AF: 0.144 AC: 503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.79
Dann	Benign	0.46

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: rs7824304; hg19: chr8-141584017;