rs2944755

Positions:

• chr8-140564095-A-G
• chr8-140564095-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012154.5(AGO2):​c.337-1461T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,232 control chromosomes in the GnomAD database, including 50,572 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 0.81 (50572 hom., cov: 34)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGO2	NM_012154.5	c.337-1461T>C		intron_variant		ENST00000220592.10	NP_036286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10	c.337-1461T>C		intron_variant		1	NM_012154.5	ENSP00000220592.5
AGO2	ENST00000519980.5	c.337-1461T>C		intron_variant		1		ENSP00000430176.1
AGO2	ENST00000523609.5	n.144-1461T>C		intron_variant		1		ENSP00000430164.1

Frequencies

GnomAD3 genomes AF: 0.809 AC: 123072 AN: 152114 Hom.: 50502 Cov.: 34

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.809 AC: 123204 AN: 152232 Hom.: 50572 Cov.: 34 AF XY: 0.814 AC XY: 60571 AN XY: 74420

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.812

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.989

Gnomad4 SAS AF: 0.859

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.782

Alfa AF: 0.749 Hom.: 24431

Bravo AF: 0.817

Asia WGS AF: 0.933 AC: 3243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.35
DANN	Benign	0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs2944755; hg19: chr8-141574194;