rs6578126

Variant names:

• chr8-140625507-G-A
• rs6578126
• NM_012154.5:c.22+9978C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-140625507-G-A
• chr8-140625507-G-C

Variant summary

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

The NM_012154.5(AGO2):​c.22+9978C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0826 in 151,926 control chromosomes in the GnomAD database, including 1,522 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 0.083 (1522 hom., cov: 33)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.779
• Publications: 1 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

LOC107986982 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.267 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.22+9978C>T		intron	N/A	NP_036286.2
	AGO2	NM_001164623.3		c.22+9978C>T		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.22+9978C>T		intron	N/A	ENSP00000220592.5	Q9UKV8-1
	AGO2	ENST00000519980.5	TSL:1	c.22+9978C>T		intron	N/A	ENSP00000430176.1	Q9UKV8-2
	AGO2	ENST00000523609.5	TSL:1	n.22+9978C>T		intron	N/A	ENSP00000430164.1	E5RGG9

Frequencies

GnomAD3 genomes AF: 0.0824 AC: 12511 AN: 151808 Hom.: 1515 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.0711

Gnomad SAS AF: 0.0235

Gnomad FIN AF: 0.00739

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00166

Gnomad OTH AF: 0.0623

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

GnomAD4 genome AF: 0.0826 AC: 12544 AN: 151926 Hom.: 1522 Cov.: 33 AF XY: 0.0805 AC XY: 5979 AN XY: 74268

African (AFR) AF: 0.271 AC: 11217 AN: 41356

American (AMR) AF: 0.0315 AC: 482 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3464

East Asian (EAS) AF: 0.0705 AC: 363 AN: 5152

South Asian (SAS) AF: 0.0235 AC: 113 AN: 4808

European-Finnish (FIN) AF: 0.00739 AC: 78 AN: 10560

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00166 AC: 113 AN: 67986

Other (OTH) AF: 0.0617 AC: 130 AN: 2108

Alfa AF: 0.0214 Hom.: 62

Bravo AF: 0.0939

Asia WGS AF: 0.0710 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.21
PhyloP100		-0.78
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6578126;

hg19: chr8-141635606;