chr8-140546044-C-T

Variant names:

• chr8-140546044-C-T
• rs12542354
• NM_012154.5:c.1748+1424G>A

Variant summary

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

The NM_012154.5(AGO2):​c.1748+1424G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0652 in 152,302 control chromosomes in the GnomAD database, including 581 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 0.065 (581 hom., cov: 33)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGO2	NM_012154.5	c.1748+1424G>A		intron_variant	Intron 13 of 18	ENST00000220592.10	NP_036286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10	c.1748+1424G>A		intron_variant	Intron 13 of 18	1	NM_012154.5	ENSP00000220592.5
AGO2	ENST00000519980.5	c.1748+1424G>A		intron_variant	Intron 13 of 17	1		ENSP00000430176.1
AGO2	ENST00000523609.5	n.*1333+1424G>A		intron_variant	Intron 12 of 17	1		ENSP00000430164.1

Frequencies

GnomAD3 genomes AF: 0.0651 AC: 9910 AN: 152184 Hom.: 573 Cov.: 33

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0576

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0612

Gnomad OTH AF: 0.0632

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

GnomAD4 genome AF: 0.0652 AC: 9936 AN: 152302 Hom.: 581 Cov.: 33 AF XY: 0.0672 AC XY: 5004 AN XY: 74478

African (AFR) AF: 0.0164 AC: 683 AN: 41576

American (AMR) AF: 0.143 AC: 2187 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3468

East Asian (EAS) AF: 0.259 AC: 1337 AN: 5170

South Asian (SAS) AF: 0.129 AC: 622 AN: 4830

European-Finnish (FIN) AF: 0.0576 AC: 612 AN: 10624

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0612 AC: 4161 AN: 68030

Other (OTH) AF: 0.0616 AC: 130 AN: 2110

Alfa AF: 0.0569 Hom.: 151

Bravo AF: 0.0729

Asia WGS AF: 0.197 AC: 684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	10
DANN	Benign	0.73
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12542354; hg19: chr8-141556143;