dbSNP rs1034809: PON2:c.145+2175C>T (chr7-95422340-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000305.3(PON2):c.145+2175C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,052 control chromosomes in the GnomAD database, including 5,523 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 0.26 ( 5523 hom., cov: 32)

Consequence

PON2
NM_000305.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.15

Publications

3 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:

LOC107986822 (HGNC:):

LOC107986822 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=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PON2	NM_000305.3 link	c.145+2175C>T	intron_variant	Intron 2 of 8	ENST00000222572.8	NP_000296.2	Q15165-2
LOC107986822	XR_007060439.1 link	n.4582G>A	non_coding_transcript_exon_variant	Exon 2 of 2
PON2	NM_001018161.2 link	c.145+2175C>T	intron_variant	Intron 2 of 8		NP_001018171.1	Q15165-3
PON2	XM_005250453.2 link	c.-34+2175C>T	intron_variant	Intron 1 of 7		XP_005250510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8 link	c.145+2175C>T		intron_variant	Intron 2 of 8	1	NM_000305.3	ENSP00000222572.3		Q15165-2

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39347

AN:

151936

Hom.:

5511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.372

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.365

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.230

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

GnomAD4 genome

AF:

0.259

AC:

39384

AN:

152052

Hom.:

5523

Cov.:

AF XY:

0.269

AC XY:

19962

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.254

AC:

10550

AN:

41498

American (AMR)

AF:

0.217

AC:

3311

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

636

AN:

3464

East Asian (EAS)

AF:

0.192

AC:

993

AN:

5176

South Asian (SAS)

AF:

0.365

AC:

1757

AN:

4816

European-Finnish (FIN)

AF:

0.451

AC:

4750

AN:

10542

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.243

AC:

16487

AN:

67948

Other (OTH)

AF:

0.234

AC:

495

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1461

2922

4384

5845

7306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<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:

0.259

Hom.:

652

Bravo

AF:

0.236

Asia WGS

AF:

0.295

AC:

1024

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.9

(source)

DANN

Benign

0.25

PhyloP100

1.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over