8-140539284-A-G

Variant names:

• chr8-140539284-A-G
• rs13252337
• NM_012154.5:c.2169+36T>C

Variant summary

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

The NM_012154.5(AGO2):​c.2169+36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,573,646 control chromosomes in the GnomAD database, including 52,217 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 0.21 (4064 hom., cov: 32)
  • Exomes 𝑓: 0.26 (48153 hom.)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGO2	NM_012154.5	c.2169+36T>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+36T>C		intron_variant	Intron 16 of 18	1	NM_012154.5	ENSP00000220592.5

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31965 AN: 151834 Hom.: 4062 Cov.: 32

Gnomad AFR AF: 0.0655

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.229

GnomAD3 exomes AF: 0.252 AC: 56075 AN: 222086 Hom.: 7628 AF XY: 0.257 AC XY: 30500 AN XY: 118692

Gnomad AFR exome AF: 0.0584

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.249

Gnomad EAS exome AF: 0.312

Gnomad SAS exome AF: 0.260

Gnomad FIN exome AF: 0.341

Gnomad NFE exome AF: 0.264

Gnomad OTH exome AF: 0.259

GnomAD4 exome AF: 0.256 AC: 363917 AN: 1421692 Hom.: 48153 Cov.: 33 AF XY: 0.257 AC XY: 180333 AN XY: 702750

Gnomad4 AFR exome AF: 0.0606

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.365

Gnomad4 SAS exome AF: 0.257

Gnomad4 FIN exome AF: 0.337

Gnomad4 NFE exome AF: 0.256

Gnomad4 OTH exome AF: 0.254

GnomAD4 genome AF: 0.210 AC: 31975 AN: 151954 Hom.: 4064 Cov.: 32 AF XY: 0.216 AC XY: 16019 AN XY: 74258

Gnomad4 AFR AF: 0.0657

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.232

Alfa AF: 0.241 Hom.: 1428

Bravo AF: 0.196

Asia WGS AF: 0.265 AC: 921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.40

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: rs13252337; hg19: chr8-141549383; COSMIC: COSV55044947;