dbSNP rs17876116: PON2:c.146-1868G>T (chr7-95418165-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000305.3(PON2):c.146-1868G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 152,268 control chromosomes in the GnomAD database, including 131 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 0.034 ( 131 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

PON2
NM_000305.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.855

Publications

2 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.034 (5179/152268) while in subpopulation AMR AF = 0.0485 (741/15292). AF 95% confidence interval is 0.0456. There are 131 homozygotes in GnomAd4. There are 2545 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 5179 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PON2	NM_000305.3 link	c.146-1868G>T	intron_variant	Intron 2 of 8	ENST00000222572.8	NP_000296.2	Q15165-2
PON2	NM_001018161.2 link	c.146-1868G>T	intron_variant	Intron 2 of 8		NP_001018171.1	Q15165-3
PON2	XM_005250453.2 link	c.-33-1868G>T	intron_variant	Intron 1 of 7		XP_005250510.1
LOC107986822	XR_007060439.1 link	n.558-151C>A	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8 link	c.146-1868G>T		intron_variant	Intron 2 of 8	1	NM_000305.3	ENSP00000222572.3		Q15165-2

Frequencies

GnomAD3 genomes

AF:

0.0341

AC:

5181

AN:

152150

Hom.:

131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00970

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.0485

Gnomad ASJ

AF:

0.0533

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0155

Gnomad FIN

AF:

0.0397

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0463

Gnomad OTH

AF:

0.0440

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0340

AC:

5179

AN:

152268

Hom.:

131

Cov.:

AF XY:

0.0342

AC XY:

2545

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00968

AC:

402

AN:

41546

American (AMR)

AF:

0.0485

AC:

741

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0533

AC:

185

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.0155

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0397

AC:

421

AN:

10614

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0464

AC:

3153

AN:

68022

Other (OTH)

AF:

0.0430

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

249

498

748

997

1246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0431

Hom.:

218

Bravo

AF:

0.0341

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.32

(source)

DANN

Benign

0.48

PhyloP100

-0.85

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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