rs2977469

Variant names:

• chr8-140539192-A-G
• rs2977469
• NM_012154.5:c.2169+128T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-140539192-A-G
• chr8-140539192-A-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.2169+128T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,344,806 control chromosomes in the GnomAD database, including 166,065 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 0.51 (20221 hom., cov: 32)
  • Exomes 𝑓: 0.49 (145844 hom.)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGO2	NM_012154.5	c.2169+128T>C		intron_variant	Intron 16 of 18	ENST00000220592.10	NP_036286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10	c.2169+128T>C		intron_variant	Intron 16 of 18	1	NM_012154.5	ENSP00000220592.5

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77939 AN: 151906 Hom.: 20176 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.511

GnomAD4 exome AF: 0.491 AC: 585531 AN: 1192782 Hom.: 145844 AF XY: 0.492 AC XY: 289156 AN XY: 587702

African (AFR) AF: 0.556 AC: 15086 AN: 27116

American (AMR) AF: 0.575 AC: 14835 AN: 25796

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 8221 AN: 18026

East Asian (EAS) AF: 0.697 AC: 25397 AN: 36444

South Asian (SAS) AF: 0.552 AC: 33394 AN: 60450

European-Finnish (FIN) AF: 0.536 AC: 21238 AN: 39620

Middle Eastern (MID) AF: 0.463 AC: 1709 AN: 3692

European-Non Finnish (NFE) AF: 0.473 AC: 441109 AN: 932170

Other (OTH) AF: 0.496 AC: 24542 AN: 49468

GnomAD4 genome AF: 0.513 AC: 78044 AN: 152024 Hom.: 20221 Cov.: 32 AF XY: 0.515 AC XY: 38291 AN XY: 74288

African (AFR) AF: 0.555 AC: 22992 AN: 41448

American (AMR) AF: 0.507 AC: 7745 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1517 AN: 3470

East Asian (EAS) AF: 0.656 AC: 3387 AN: 5160

South Asian (SAS) AF: 0.546 AC: 2636 AN: 4824

European-Finnish (FIN) AF: 0.538 AC: 5684 AN: 10566

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32417 AN: 67962

Other (OTH) AF: 0.509 AC: 1076 AN: 2114

Alfa AF: 0.485 Hom.: 30646

Bravo AF: 0.518

Asia WGS AF: 0.600 AC: 2085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.67
PhyloP100		-2.0
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: rs2977469; hg19: chr8-141549291;