8-140587112-A-G

Variant names:

• chr8-140587112-A-G
• rs7819727
• NM_012154.5:c.23-1801T>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.23-1801T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,036 control chromosomes in the GnomAD database, including 47,682 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 0.79 (47682 hom., cov: 31)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.823 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.23-1801T>C		intron	N/A	NP_036286.2
	AGO2	NM_001164623.3		c.23-1801T>C		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.23-1801T>C		intron	N/A	ENSP00000220592.5
	AGO2	ENST00000519980.5	TSL:1	c.23-1801T>C		intron	N/A	ENSP00000430176.1
	AGO2	ENST00000523609.5	TSL:1	n.23-14180T>C		intron	N/A	ENSP00000430164.1

Frequencies

GnomAD3 genomes AF: 0.790 AC: 119940 AN: 151918 Hom.: 47642 Cov.: 31

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.820

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.790 AC: 120033 AN: 152036 Hom.: 47682 Cov.: 31 AF XY: 0.787 AC XY: 58462 AN XY: 74296

African (AFR) AF: 0.755 AC: 31262 AN: 41434

American (AMR) AF: 0.835 AC: 12761 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2873 AN: 3464

East Asian (EAS) AF: 0.558 AC: 2875 AN: 5150

South Asian (SAS) AF: 0.755 AC: 3634 AN: 4814

European-Finnish (FIN) AF: 0.766 AC: 8090 AN: 10568

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.820 AC: 55774 AN: 68008

Other (OTH) AF: 0.813 AC: 1718 AN: 2114

Alfa AF: 0.801 Hom.: 5728

Bravo AF: 0.791

Asia WGS AF: 0.680 AC: 2368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.23
PhyloP100		-0.26
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: rs7819727; hg19: chr8-141597211;