8-140612438-C-T

Variant names:

• chr8-140612438-C-T
• rs2176397
• NM_012154.5:c.22+23047G>A

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+23047G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,834 control chromosomes in the GnomAD database, including 7,569 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 0.31 (7569 hom., cov: 31)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640
• Publications: 9 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.392 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+23047G>A		intron	N/A	NP_036286.2
	AGO2	NM_001164623.3		c.22+23047G>A		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+23047G>A		intron	N/A	ENSP00000220592.5	Q9UKV8-1
	AGO2	ENST00000519980.5	TSL:1	c.22+23047G>A		intron	N/A	ENSP00000430176.1	Q9UKV8-2
	AGO2	ENST00000523609.5	TSL:1	n.22+23047G>A		intron	N/A	ENSP00000430164.1	E5RGG9

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47130 AN: 151716 Hom.: 7560 Cov.: 31

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.311 AC: 47167 AN: 151834 Hom.: 7569 Cov.: 31 AF XY: 0.310 AC XY: 22990 AN XY: 74212

African (AFR) AF: 0.340 AC: 14057 AN: 41364

American (AMR) AF: 0.401 AC: 6106 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1095 AN: 3468

East Asian (EAS) AF: 0.116 AC: 598 AN: 5142

South Asian (SAS) AF: 0.330 AC: 1592 AN: 4826

European-Finnish (FIN) AF: 0.253 AC: 2666 AN: 10534

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 20000 AN: 67952

Other (OTH) AF: 0.307 AC: 647 AN: 2106

Alfa AF: 0.296 Hom.: 21196

Bravo AF: 0.317

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.9
DANN	Benign	0.54
PhyloP100		-0.64
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: rs2176397; hg19: chr8-141622537;