Genetic Variant AGO2:c.2169+36T>C (chr8-140539284-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012154.5(AGO2):c.2169+36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,573,646 control chromosomes in the GnomAD database, including 52,217 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 0.21 ( 4064 hom., cov: 32)

Exomes 𝑓: 0.26 ( 48153 hom. )

Consequence

AGO2
NM_012154.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.83

Publications

6 publications found

Variant links:

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

AGO2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGO2	NM_012154.5 link	c.2169+36T>C		intron_variant	Intron 16 of 18	ENST00000220592.10	NP_036286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGO2	ENST00000220592.10 link	c.2169+36T>C		intron_variant	Intron 16 of 18	1	NM_012154.5	ENSP00000220592.5		Q9UKV8-1

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

31965

AN:

151834

Hom.:

4062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0655

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.253

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.262

Gnomad OTH

AF:

0.229

GnomAD2 exomes

AF:

0.252

AC:

56075

AN:

222086

AF XY:

0.257

show subpopulations

Gnomad AFR exome

AF:

0.0584

Gnomad AMR exome

AF:

0.218

Gnomad ASJ exome

AF:

0.249

Gnomad EAS exome

AF:

0.312

Gnomad FIN exome

AF:

0.341

Gnomad NFE exome

AF:

0.264

Gnomad OTH exome

AF:

0.259

GnomAD4 exome

AF:

0.256

AC:

363917

AN:

1421692

Hom.:

48153

Cov.:

AF XY:

0.257

AC XY:

180333

AN XY:

702750

show subpopulations

African (AFR)

AF:

0.0606

AC:

1972

AN:

32564

American (AMR)

AF:

0.223

AC:

9098

AN:

40750

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

5863

AN:

23442

East Asian (EAS)

AF:

0.365

AC:

14300

AN:

39218

South Asian (SAS)

AF:

0.257

AC:

20555

AN:

80042

European-Finnish (FIN)

AF:

0.337

AC:

17468

AN:

51780

Middle Eastern (MID)

AF:

0.205

AC:

1141

AN:

5554

European-Non Finnish (NFE)

AF:

0.256

AC:

278640

AN:

1089698

Other (OTH)

AF:

0.254

AC:

14880

AN:

58644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

12310

24619

36929

49238

61548

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9452

18904

28356

37808

47260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.210

AC:

31975

AN:

151954

Hom.:

4064

Cov.:

AF XY:

0.216

AC XY:

16019

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.0657

AC:

2726

AN:

41480

American (AMR)

AF:

0.221

AC:

3374

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

829

AN:

3470

East Asian (EAS)

AF:

0.317

AC:

1632

AN:

5152

South Asian (SAS)

AF:

0.253

AC:

1219

AN:

4814

European-Finnish (FIN)

AF:

0.337

AC:

3558

AN:

10548

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.262

AC:

17792

AN:

67910

Other (OTH)

AF:

0.232

AC:

491

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1252

2504

3756

5008

6260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.241

Hom.:

1428

Bravo

AF:

0.196

Asia WGS

AF:

0.265

AC:

921

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.1

(source)

DANN

Benign

0.40

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over