rs7824304

Variant names:

• chr8-140573918-C-T
• rs7824304
• NM_012154.5:c.216-986G>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.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
• 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=-0.99).
• 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 rank	MANE	Protein	UniProt
AGO2	NM_012154.5	c.216-986G>A		intron_variant	Intron 2 of 18	ENST00000220592.10	NP_036286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10	c.216-986G>A		intron_variant	Intron 2 of 18	1	NM_012154.5	ENSP00000220592.5

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

African (AFR) AF: 0.268 AC: 11111 AN: 41474

American (AMR) AF: 0.256 AC: 3912 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1377 AN: 3468

East Asian (EAS) AF: 0.0409 AC: 212 AN: 5178

South Asian (SAS) AF: 0.283 AC: 1366 AN: 4828

European-Finnish (FIN) AF: 0.255 AC: 2692 AN: 10572

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21814 AN: 67980

Other (OTH) AF: 0.306 AC: 646 AN: 2114

Alfa AF: 0.320 Hom.: 13280

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
PhyloP100		-1.9
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: rs7824304; hg19: chr8-141584017;