rs7001653

Variant names:

• chr8-140610939-G-A
• rs7001653
• NM_012154.5:c.22+24546C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-140610939-G-A
• chr8-140610939-G-C
• chr8-140610939-G-T

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+24546C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,142 control chromosomes in the GnomAD database, including 13,783 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 0.42 (13783 hom., cov: 33)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 5 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

ENSG00000303049 (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 (NFE) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGO2	NM_012154.5	c.22+24546C>T		intron_variant	Intron 1 of 18	ENST00000220592.10	NP_036286.2
AGO2	NM_001164623.3	c.22+24546C>T		intron_variant	Intron 1 of 17		NP_001158095.1
AGO2	XM_011516968.3	c.-116-25628C>T		intron_variant	Intron 1 of 18		XP_011515270.3
AGO2	XM_047421697.1	c.-234-5025C>T		intron_variant	Intron 1 of 19		XP_047277653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10	c.22+24546C>T		intron_variant	Intron 1 of 18	1	NM_012154.5	ENSP00000220592.5

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63863 AN: 152024 Hom.: 13778 Cov.: 33

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.420 AC: 63895 AN: 152142 Hom.: 13783 Cov.: 33 AF XY: 0.419 AC XY: 31198 AN XY: 74396

African (AFR) AF: 0.311 AC: 12889 AN: 41510

American (AMR) AF: 0.401 AC: 6127 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1636 AN: 3470

East Asian (EAS) AF: 0.440 AC: 2278 AN: 5174

South Asian (SAS) AF: 0.402 AC: 1941 AN: 4830

European-Finnish (FIN) AF: 0.454 AC: 4804 AN: 10588

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.480 AC: 32603 AN: 67976

Other (OTH) AF: 0.452 AC: 953 AN: 2108

Alfa AF: 0.462 Hom.: 27654

Bravo AF: 0.415

Asia WGS AF: 0.422 AC: 1467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.72
PhyloP100		0.015
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: rs7001653; hg19: chr8-141621038;