rs7005286

Variant names:

• chr8-140584361-T-C
• rs7005286
• NM_012154.5:c.215+758A>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.215+758A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 152,088 control chromosomes in the GnomAD database, including 55,711 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 0.85 (55711 hom., cov: 30)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.78
• Publications: 6 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012154.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGO2	NM_012154.5	MANE Select	c.215+758A>G		intron	N/A	NP_036286.2
	AGO2	NM_001164623.3		c.215+758A>G		intron	N/A	NP_001158095.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGO2	ENST00000220592.10	TSL:1 MANE Select	c.215+758A>G		intron	N/A	ENSP00000220592.5
	AGO2	ENST00000519980.5	TSL:1	c.215+758A>G		intron	N/A	ENSP00000430176.1
	AGO2	ENST00000523609.5	TSL:1	n.23-11429A>G		intron	N/A	ENSP00000430164.1

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129864 AN: 151970 Hom.: 55656 Cov.: 30

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.789

Gnomad MID AF: 0.828

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.860

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

GnomAD4 genome AF: 0.855 AC: 129974 AN: 152088 Hom.: 55711 Cov.: 30 AF XY: 0.852 AC XY: 63328 AN XY: 74352

African (AFR) AF: 0.911 AC: 37782 AN: 41490

American (AMR) AF: 0.854 AC: 13057 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3096 AN: 3472

East Asian (EAS) AF: 0.692 AC: 3564 AN: 5154

South Asian (SAS) AF: 0.839 AC: 4031 AN: 4806

European-Finnish (FIN) AF: 0.789 AC: 8345 AN: 10574

Middle Eastern (MID) AF: 0.836 AC: 244 AN: 292

European-Non Finnish (NFE) AF: 0.841 AC: 57152 AN: 67992

Other (OTH) AF: 0.862 AC: 1825 AN: 2116

Alfa AF: 0.846 Hom.: 23803

Bravo AF: 0.861

Asia WGS AF: 0.777 AC: 2701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.012
DANN	Benign	0.18
PhyloP100		-2.8
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: rs7005286; hg19: chr8-141594460;