chr8-140584782-T-C

Variant names:

• chr8-140584782-T-C
• rs7009635
• NM_012154.5:c.215+337A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012154.5(AGO2):​c.215+337A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,920 control chromosomes in the GnomAD database, including 16,909 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 0.43 (16909 hom., cov: 31)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012154.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGO2	NM_012154.5	MANE Select	c.215+337A>G		intron	N/A	NP_036286.2
	AGO2	NM_001164623.3		c.215+337A>G		intron	N/A	NP_001158095.1	Q9UKV8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGO2	ENST00000220592.10	TSL:1 MANE Select	c.215+337A>G		intron	N/A	ENSP00000220592.5	Q9UKV8-1
	AGO2	ENST00000519980.5	TSL:1	c.215+337A>G		intron	N/A	ENSP00000430176.1	Q9UKV8-2
	AGO2	ENST00000523609.5	TSL:1	n.23-11850A>G		intron	N/A	ENSP00000430164.1	E5RGG9

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65162 AN: 151802 Hom.: 16908 Cov.: 31

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.429 AC: 65159 AN: 151920 Hom.: 16909 Cov.: 31 AF XY: 0.424 AC XY: 31482 AN XY: 74234

African (AFR) AF: 0.144 AC: 5987 AN: 41446

American (AMR) AF: 0.389 AC: 5931 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1674 AN: 3470

East Asian (EAS) AF: 0.375 AC: 1938 AN: 5172

South Asian (SAS) AF: 0.392 AC: 1881 AN: 4804

European-Finnish (FIN) AF: 0.527 AC: 5547 AN: 10534

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.595 AC: 40413 AN: 67924

Other (OTH) AF: 0.480 AC: 1009 AN: 2104

Alfa AF: 0.541 Hom.: 39653

Bravo AF: 0.409

Asia WGS AF: 0.379 AC: 1318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.011
DANN	Benign	0.23
PhyloP100		-2.8
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: rs7009635; hg19: chr8-141594881;