rs11982486

Variant names:

• chr7-95426286-T-C
• rs11982486
• NM_000305.3:c.75-1701A>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.75-1701A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,078 control chromosomes in the GnomAD database, including 6,868 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 0.29 (6868 hom., cov: 32)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 6 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 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.75-1701A>G		intron	N/A	NP_000296.2	Q15165-2
	PON2	NM_001018161.2		c.75-1701A>G		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.75-1701A>G		intron	N/A	ENSP00000222572.3	Q15165-2
	PON2	ENST00000633192.1	TSL:1	c.138-1701A>G		intron	N/A	ENSP00000488378.1	A0A0J9YXF2
	PON2	ENST00000633531.1	TSL:1	c.75-1701A>G		intron	N/A	ENSP00000488838.1	Q15165-2

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44131 AN: 151960 Hom.: 6868 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.00519

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.290 AC: 44146 AN: 152078 Hom.: 6868 Cov.: 32 AF XY: 0.278 AC XY: 20679 AN XY: 74352

African (AFR) AF: 0.279 AC: 11572 AN: 41480

American (AMR) AF: 0.216 AC: 3305 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1276 AN: 3470

East Asian (EAS) AF: 0.00521 AC: 27 AN: 5186

South Asian (SAS) AF: 0.219 AC: 1054 AN: 4816

European-Finnish (FIN) AF: 0.227 AC: 2397 AN: 10572

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.347 AC: 23568 AN: 67970

Other (OTH) AF: 0.294 AC: 619 AN: 2108

Alfa AF: 0.326 Hom.: 10450

Bravo AF: 0.285

Asia WGS AF: 0.111 AC: 390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.14
DANN	Benign	0.61
PhyloP100		-2.3
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11982486;

hg19: chr7-95055598;