rs987539

Variant names:

• chr7-95407680-C-T
• rs987539
• NM_000305.3:c.696-612G>A

Variant summary

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

The NM_000305.3(PON2):​c.696-612G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,976 control chromosomes in the GnomAD database, including 24,336 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 0.55 (24336 hom., cov: 32)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660
• Publications: 17 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

ENSG00000233942 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000305.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PON2	NM_000305.3	MANE Select	c.696-612G>A		intron	N/A	NP_000296.2	Q15165-2
	PON2	NM_001018161.2		c.660-612G>A		intron	N/A	NP_001018171.1	Q15165-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PON2	ENST00000222572.8	TSL:1 MANE Select	c.696-612G>A		intron	N/A	ENSP00000222572.3	Q15165-2
	PON2	ENST00000633192.1	TSL:1	c.759-612G>A		intron	N/A	ENSP00000488378.1	A0A0J9YXF2
	PON2	ENST00000633531.1	TSL:1	c.696-612G>A		intron	N/A	ENSP00000488838.1	Q15165-2

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84182 AN: 151858 Hom.: 24292 Cov.: 32

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.555 AC: 84289 AN: 151976 Hom.: 24336 Cov.: 32 AF XY: 0.568 AC XY: 42203 AN XY: 74236

African (AFR) AF: 0.645 AC: 26737 AN: 41440

American (AMR) AF: 0.626 AC: 9552 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1335 AN: 3470

East Asian (EAS) AF: 0.834 AC: 4313 AN: 5172

South Asian (SAS) AF: 0.689 AC: 3314 AN: 4812

European-Finnish (FIN) AF: 0.630 AC: 6640 AN: 10534

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30689 AN: 67966

Other (OTH) AF: 0.526 AC: 1111 AN: 2114

Alfa AF: 0.477 Hom.: 21015

Bravo AF: 0.558

Asia WGS AF: 0.756 AC: 2627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.27
DANN	Benign	0.13
PhyloP100		-0.66
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: rs987539; hg19: chr7-95036992;