8-140551758-C-G

Variant names:

• chr8-140551758-C-G
• rs2977481
• NM_012154.5:c.1270-322G>C

Variant summary

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

The NM_012154.5(AGO2):​c.1270-322G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 142,094 control chromosomes in the GnomAD database, including 33,138 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 0.68 (33138 hom., cov: 24)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.46
• Publications: 3 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: Labcorp Genetics (formerly Invitae), Illumina, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGO2	NM_012154.5	MANE Select	c.1270-322G>C		intron	N/A	NP_036286.2
	AGO2	NM_001164623.3		c.1270-322G>C		intron	N/A	NP_001158095.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGO2	ENST00000220592.10	TSL:1 MANE Select	c.1270-322G>C		intron	N/A	ENSP00000220592.5
	AGO2	ENST00000519980.5	TSL:1	c.1270-322G>C		intron	N/A	ENSP00000430176.1
	AGO2	ENST00000523609.5	TSL:1	n.*855-322G>C		intron	N/A	ENSP00000430164.1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 96471 AN: 141980 Hom.: 33073 Cov.: 24

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.711

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.626

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.680 AC: 96596 AN: 142094 Hom.: 33138 Cov.: 24 AF XY: 0.683 AC XY: 47075 AN XY: 68878

African (AFR) AF: 0.890 AC: 35810 AN: 40218

American (AMR) AF: 0.712 AC: 10353 AN: 14540

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 1915 AN: 3294

East Asian (EAS) AF: 0.726 AC: 3400 AN: 4686

South Asian (SAS) AF: 0.670 AC: 2966 AN: 4424

European-Finnish (FIN) AF: 0.564 AC: 4945 AN: 8762

Middle Eastern (MID) AF: 0.641 AC: 177 AN: 276

European-Non Finnish (NFE) AF: 0.561 AC: 35413 AN: 63166

Other (OTH) AF: 0.656 AC: 1281 AN: 1954

Alfa AF: 0.397 Hom.: 913

Bravo AF: 0.676

Asia WGS AF: 0.680 AC: 2322 AN: 3416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.18
PhyloP100		-3.5
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: rs2977481; hg19: chr8-141561857;