rs2977490

Variant names:

• chr8-140563259-G-A
• rs2977490
• NM_012154.5:c.337-625C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-140563259-G-A
• chr8-140563259-G-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.337-625C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,040 control chromosomes in the GnomAD database, including 19,643 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 0.50 (19643 hom., cov: 33)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGO2	NM_012154.5	c.337-625C>T		intron_variant	Intron 3 of 18	ENST00000220592.10	NP_036286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10	c.337-625C>T		intron_variant	Intron 3 of 18	1	NM_012154.5	ENSP00000220592.5
AGO2	ENST00000519980.5	c.337-625C>T		intron_variant	Intron 3 of 17	1		ENSP00000430176.1
AGO2	ENST00000523609.5	n.144-625C>T		intron_variant	Intron 2 of 17	1		ENSP00000430164.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76495 AN: 151922 Hom.: 19619 Cov.: 33

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.504 AC: 76569 AN: 152040 Hom.: 19643 Cov.: 33 AF XY: 0.502 AC XY: 37322 AN XY: 74316

African (AFR) AF: 0.599 AC: 24827 AN: 41476

American (AMR) AF: 0.383 AC: 5856 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1315 AN: 3472

East Asian (EAS) AF: 0.583 AC: 3007 AN: 5162

South Asian (SAS) AF: 0.464 AC: 2233 AN: 4814

European-Finnish (FIN) AF: 0.520 AC: 5486 AN: 10554

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32115 AN: 67966

Other (OTH) AF: 0.491 AC: 1035 AN: 2110

Alfa AF: 0.475 Hom.: 52677

Bravo AF: 0.499

Asia WGS AF: 0.520 AC: 1807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.81
PhyloP100		-0.12
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: rs2977490; hg19: chr8-141573358;