8-140619298-A-G

Variant names:

• chr8-140619298-A-G
• rs13261055
• NM_012154.5:c.22+16187T>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.22+16187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,152 control chromosomes in the GnomAD database, including 15,800 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 0.44 (15800 hom., cov: 33)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.385
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGO2	NM_012154.5	c.22+16187T>C		intron_variant	Intron 1 of 18	ENST00000220592.10	NP_036286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10	c.22+16187T>C		intron_variant	Intron 1 of 18	1	NM_012154.5	ENSP00000220592.5

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67355 AN: 152034 Hom.: 15794 Cov.: 33

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.443 AC: 67375 AN: 152152 Hom.: 15800 Cov.: 33 AF XY: 0.439 AC XY: 32675 AN XY: 74396

African (AFR) AF: 0.285 AC: 11824 AN: 41510

American (AMR) AF: 0.427 AC: 6526 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1902 AN: 3470

East Asian (EAS) AF: 0.366 AC: 1894 AN: 5174

South Asian (SAS) AF: 0.426 AC: 2053 AN: 4824

European-Finnish (FIN) AF: 0.468 AC: 4955 AN: 10582

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36512 AN: 67978

Other (OTH) AF: 0.485 AC: 1027 AN: 2116

Alfa AF: 0.360 Hom.: 1032

Bravo AF: 0.436

Asia WGS AF: 0.380 AC: 1323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.50
PhyloP100		0.39
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: rs13261055; hg19: chr8-141629397;