GeneBe

chr8-140532105-T-TG

Position:

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_012154.5(AGO2):​c.2518_2519insC​(p.Gln840ProfsTer27) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

AGO2
NM_012154.5 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.94
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.024 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AGO2NM_012154.5 linkuse as main transcriptc.2518_2519insC p.Gln840ProfsTer27 frameshift_variant 19/19 ENST00000220592.10 NP_036286.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AGO2ENST00000220592.10 linkuse as main transcriptc.2518_2519insC p.Gln840ProfsTer27 frameshift_variant 19/191 NM_012154.5 ENSP00000220592 P1Q9UKV8-1
AGO2ENST00000519980.5 linkuse as main transcriptc.2416_2417insC p.Gln806ProfsTer27 frameshift_variant 18/181 ENSP00000430176 Q9UKV8-2
AGO2ENST00000523609.5 linkuse as main transcriptc.*2103_*2104insC 3_prime_UTR_variant, NMD_transcript_variant 18/181 ENSP00000430164
AGO2ENST00000520628.1 linkuse as main transcriptn.338_339insC non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-141542204; API