chr8-140620073-G-A

Variant names:

• chr8-140620073-G-A
• rs11786030
• NM_012154.5:c.22+15412C>T

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+15412C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 152,120 control chromosomes in the GnomAD database, including 52,233 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 0.83 (52233 hom., cov: 32)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436
• Publications: 13 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

LOC107986982 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.85 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+15412C>T		intron	N/A	NP_036286.2
	AGO2	NM_001164623.3		c.22+15412C>T		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+15412C>T		intron	N/A	ENSP00000220592.5
	AGO2	ENST00000519980.5	TSL:1	c.22+15412C>T		intron	N/A	ENSP00000430176.1
	AGO2	ENST00000523609.5	TSL:1	n.22+15412C>T		intron	N/A	ENSP00000430164.1

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125499 AN: 152000 Hom.: 52174 Cov.: 32

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.946

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.846

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

GnomAD4 genome AF: 0.826 AC: 125616 AN: 152120 Hom.: 52233 Cov.: 32 AF XY: 0.821 AC XY: 61059 AN XY: 74352

African (AFR) AF: 0.856 AC: 35541 AN: 41500

American (AMR) AF: 0.862 AC: 13188 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3103 AN: 3468

East Asian (EAS) AF: 0.558 AC: 2872 AN: 5146

South Asian (SAS) AF: 0.787 AC: 3791 AN: 4820

European-Finnish (FIN) AF: 0.726 AC: 7679 AN: 10576

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.831 AC: 56543 AN: 68002

Other (OTH) AF: 0.848 AC: 1787 AN: 2108

Alfa AF: 0.836 Hom.: 108043

Bravo AF: 0.835

Asia WGS AF: 0.705 AC: 2453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.42
DANN	Benign	0.65
PhyloP100		-0.44
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: rs11786030; hg19: chr8-141630172;