rs2158806

Variant names:

• chr7-95422686-A-C
• rs2158806
• NM_000305.3:c.145+1829T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000305.3(PON2):​c.145+1829T>G 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 152,118 control chromosomes in the GnomAD database, including 5,518 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 (5518 hom., cov: 32)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491
• Publications: 4 publications found

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

LOC107986822 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON2	NM_000305.3	c.145+1829T>G		intron_variant	Intron 2 of 8	ENST00000222572.8	NP_000296.2
LOC107986822	XR_007060439.1	n.4928A>C		non_coding_transcript_exon_variant	Exon 2 of 2
PON2	NM_001018161.2	c.145+1829T>G		intron_variant	Intron 2 of 8		NP_001018171.1
PON2	XM_005250453.2	c.-34+1829T>G		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	c.145+1829T>G		intron_variant	Intron 2 of 8	1	NM_000305.3	ENSP00000222572.3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39345 AN: 152000 Hom.: 5506 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.232

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: 39382 AN: 152118 Hom.: 5518 Cov.: 32 AF XY: 0.268 AC XY: 19961 AN XY: 74368

African (AFR) AF: 0.254 AC: 10545 AN: 41514

American (AMR) AF: 0.216 AC: 3309 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 639 AN: 3466

East Asian (EAS) AF: 0.191 AC: 990 AN: 5176

South Asian (SAS) AF: 0.365 AC: 1758 AN: 4822

European-Finnish (FIN) AF: 0.450 AC: 4745 AN: 10548

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.243 AC: 16497 AN: 67978

Other (OTH) AF: 0.234 AC: 496 AN: 2116

Alfa AF: 0.234 Hom.: 4720

Bravo AF: 0.236

Asia WGS AF: 0.297 AC: 1028 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.85
DANN	Benign	0.50
PhyloP100		-0.49
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: rs2158806; hg19: chr7-95051998;