rs2299267

Positions:

• chr7-95432609-A-G
• chr7-95432609-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000305.3(PON2):​c.74+2269T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,108 control chromosomes in the GnomAD database, including 2,204 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 0.16 (2204 hom., cov: 32)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON2	NM_000305.3	c.74+2269T>C		intron_variant		ENST00000222572.8	NP_000296.2
PON2	NM_001018161.2	c.74+2269T>C		intron_variant			NP_001018171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8	c.74+2269T>C		intron_variant		1	NM_000305.3	ENSP00000222572	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24656 AN: 151990 Hom.: 2203 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.162 AC: 24661 AN: 152108 Hom.: 2204 Cov.: 32 AF XY: 0.165 AC XY: 12250 AN XY: 74342

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.187

Alfa AF: 0.166 Hom.: 3077

Bravo AF: 0.169

Asia WGS AF: 0.289 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.0
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs2299267; hg19: chr7-95061921;