8-140630195-T-C

Variant names:

• chr8-140630195-T-C
• rs10088596
• NM_012154.5:c.22+5290A>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.22+5290A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 152,142 control chromosomes in the GnomAD database, including 36,652 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 0.69 (36652 hom., cov: 33)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.457
• 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: Illumina, Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000303049 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.762 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.22+5290A>G		intron	N/A	NP_036286.2
	AGO2	NM_001164623.3		c.22+5290A>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.22+5290A>G		intron	N/A	ENSP00000220592.5
	AGO2	ENST00000519980.5	TSL:1	c.22+5290A>G		intron	N/A	ENSP00000430176.1
	AGO2	ENST00000523609.5	TSL:1	n.22+5290A>G		intron	N/A	ENSP00000430164.1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104964 AN: 152024 Hom.: 36620 Cov.: 33

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.690 AC: 105048 AN: 152142 Hom.: 36652 Cov.: 33 AF XY: 0.691 AC XY: 51364 AN XY: 74368

African (AFR) AF: 0.638 AC: 26472 AN: 41498

American (AMR) AF: 0.774 AC: 11828 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2773 AN: 3468

East Asian (EAS) AF: 0.477 AC: 2464 AN: 5170

South Asian (SAS) AF: 0.685 AC: 3301 AN: 4822

European-Finnish (FIN) AF: 0.657 AC: 6942 AN: 10570

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48835 AN: 68006

Other (OTH) AF: 0.715 AC: 1513 AN: 2116

Alfa AF: 0.712 Hom.: 19606

Bravo AF: 0.695

Asia WGS AF: 0.592 AC: 2062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.46
PhyloP100		0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs10088596; hg19: chr8-141640294;