rs7493

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000305.3(PON2):c.932C>G(p.Ser311Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,611,536 control chromosomes in the GnomAD database, including 54,604 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5893 hom., cov: 32)

Exomes 𝑓: 0.25 ( 48711 hom. )

Consequence

PON2
NM_000305.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 9.26

Publications

204 publications found

Variant links:

Genes affected

PON2 (HGNC:9205): (paraoxonase 2) This gene encodes a member of the paraoxonase gene family, which includes three known members located adjacent to each other on the long arm of chromosome 7. The encoded protein is ubiquitously expressed in human tissues, membrane-bound, and may act as a cellular antioxidant, protecting cells from oxidative stress. Hydrolytic activity against acylhomoserine lactones, important bacterial quorum-sensing mediators, suggests the encoded protein may also play a role in defense responses to pathogenic bacteria. Mutations in this gene may be associated with vascular disease and a number of quantitative phenotypes related to diabetes. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

PON2 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PON2 links:

ENSG00000233942 (HGNC:):

ENSG00000233942 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030953884).

BP6

Variant 7-95405463-G-C is Benign according to our data. Variant chr7-95405463-G-C is described in ClinVar as Benign. ClinVar VariationId is 7084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON2	NM_000305.3 link	c.932C>G	p.Ser311Cys	missense_variant	Exon 9 of 9	ENST00000222572.8	NP_000296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8 link	c.932C>G	p.Ser311Cys	missense_variant	Exon 9 of 9	1	NM_000305.3	ENSP00000222572.3

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40743

AN:

151836

Hom.:

5877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.287

Gnomad AMI

AF:

0.372

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.450

Gnomad MID

AF:

0.239

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.236

GnomAD2 exomes

AF:

0.268

AC:

66761

AN:

249520

AF XY:

0.274

show subpopulations

Gnomad AFR exome

AF:

0.296

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.174

Gnomad EAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.434

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.251

GnomAD4 exome

AF:

0.253

AC:

368864

AN:

1459582

Hom.:

48711

Cov.:

AF XY:

0.257

AC XY:

186294

AN XY:

726236

show subpopulations

African (AFR)

AF:

0.299

AC:

9996

AN:

33410

American (AMR)

AF:

0.213

AC:

9538

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

4613

AN:

26116

East Asian (EAS)

AF:

0.197

AC:

7830

AN:

39676

South Asian (SAS)

AF:

0.363

AC:

31294

AN:

86202

European-Finnish (FIN)

AF:

0.426

AC:

22744

AN:

53398

Middle Eastern (MID)

AF:

0.246

AC:

1415

AN:

5760

European-Non Finnish (NFE)

AF:

0.240

AC:

266191

AN:

1109984

Other (OTH)

AF:

0.253

AC:

15243

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

13896

27792

41688

55584

69480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9102

18204

27306

36408

45510

<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:

0.268

AC:

40788

AN:

151954

Hom.:

5893

Cov.:

AF XY:

0.277

AC XY:

20602

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.287

AC:

11907

AN:

41424

American (AMR)

AF:

0.220

AC:

3360

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

640

AN:

3472

East Asian (EAS)

AF:

0.192

AC:

991

AN:

5166

South Asian (SAS)

AF:

0.364

AC:

1747

AN:

4804

European-Finnish (FIN)

AF:

0.450

AC:

4730

AN:

10518

Middle Eastern (MID)

AF:

0.226

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.243

AC:

16502

AN:

67986

Other (OTH)

AF:

0.240

AC:

507

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1478

2956

4434

5912

7390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

418

836

1254

1672

2090

<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:

0.235

Hom.:

3321

Bravo

AF:

0.246

TwinsUK

AF:

0.241

AC:

894

ALSPAC

AF:

0.245

AC:

944

ESP6500AA

AF:

0.284

AC:

1250

ESP6500EA

AF:

0.228

AC:

1961

ExAC

AF:

0.271

AC:

32895

Asia WGS

AF:

0.299

AC:

1040

AN:

3478

EpiCase

AF:

0.230

EpiControl

AF:

0.233

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 18759523, 21303902, 19930448, 19840942, 23225229, 19540141, 9443862) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

PARAOXONASE 2 POLYMORPHISM

Benign:1

Jan 01, 1998

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Benign

0.96

Eigen

Benign

-0.11

Eigen_PC

Benign

0.020

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.59

T;T;.;T

MetaRNN

Benign

0.0031

T;T;T;T

MetaSVM

Benign

-0.99

PhyloP100

9.3

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.5

.;D;D;.

REVEL

Benign

0.18

Sift

Uncertain

0.022

.;D;D;.

Sift4G

Uncertain

0.052

T;T;T;T

Vest4

0.29

MPC

0.090

ClinPred

0.15

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

gMVP

0.65

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over