8-140603795-T-C

Variant names:

• chr8-140603795-T-C
• rs7016981
• NM_012154.5:c.23-18484A>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.23-18484A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,146 control chromosomes in the GnomAD database, including 9,861 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 0.35 (9861 hom., cov: 33)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGO2	NM_012154.5	c.23-18484A>G		intron_variant	Intron 1 of 18	ENST00000220592.10	NP_036286.2
AGO2	NM_001164623.3	c.23-18484A>G		intron_variant	Intron 1 of 17		NP_001158095.1
AGO2	XM_011516968.3	c.-116-18484A>G		intron_variant	Intron 1 of 18		XP_011515270.3
AGO2	XM_047421697.1	c.-117+2002A>G		intron_variant	Intron 2 of 19		XP_047277653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10	c.23-18484A>G		intron_variant	Intron 1 of 18	1	NM_012154.5	ENSP00000220592.5

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53081 AN: 152028 Hom.: 9842 Cov.: 33

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.349 AC: 53147 AN: 152146 Hom.: 9861 Cov.: 33 AF XY: 0.348 AC XY: 25863 AN XY: 74376

African (AFR) AF: 0.458 AC: 19005 AN: 41490

American (AMR) AF: 0.412 AC: 6301 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1157 AN: 3472

East Asian (EAS) AF: 0.116 AC: 601 AN: 5176

South Asian (SAS) AF: 0.346 AC: 1672 AN: 4828

European-Finnish (FIN) AF: 0.257 AC: 2728 AN: 10602

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20588 AN: 67974

Other (OTH) AF: 0.334 AC: 706 AN: 2116

Alfa AF: 0.324 Hom.: 1680

Bravo AF: 0.360

Asia WGS AF: 0.252 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.6
DANN	Benign	0.54
PhyloP100		-0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7016981; hg19: chr8-141613894;