rs2286233

Variant names:

• chr7-95424945-T-A
• rs2286233
• NM_000305.3:c.75-360A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-95424945-T-A
• chr7-95424945-T-C
• chr7-95424945-T-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.75-360A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,136 control chromosomes in the GnomAD database, including 55,296 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 0.85 (55296 hom., cov: 31)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.9 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PON2	NM_000305.3	MANE Select	c.75-360A>T		intron	N/A	NP_000296.2
	PON2	NM_001018161.2		c.75-360A>T		intron	N/A	NP_001018171.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PON2	ENST00000222572.8	TSL:1 MANE Select	c.75-360A>T		intron	N/A	ENSP00000222572.3
	PON2	ENST00000633192.1	TSL:1	c.138-360A>T		intron	N/A	ENSP00000488378.1
	PON2	ENST00000633531.1	TSL:1	c.75-360A>T		intron	N/A	ENSP00000488838.1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129345 AN: 152018 Hom.: 55250 Cov.: 31

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.854

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

GnomAD4 genome AF: 0.851 AC: 129448 AN: 152136 Hom.: 55296 Cov.: 31 AF XY: 0.856 AC XY: 63632 AN XY: 74374

African (AFR) AF: 0.768 AC: 31861 AN: 41472

American (AMR) AF: 0.899 AC: 13749 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2971 AN: 3472

East Asian (EAS) AF: 0.837 AC: 4325 AN: 5168

South Asian (SAS) AF: 0.923 AC: 4444 AN: 4816

European-Finnish (FIN) AF: 0.901 AC: 9547 AN: 10598

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.878 AC: 59682 AN: 68004

Other (OTH) AF: 0.856 AC: 1807 AN: 2110

Alfa AF: 0.833 Hom.: 2621

Bravo AF: 0.848

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.1
DANN	Benign	0.52
PhyloP100		0.22
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: rs2286233; hg19: chr7-95054257;