rs730365

chr7-95433688-C-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+1190G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,212 control chromosomes in the GnomAD database, including 1,927 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 0.15 (1927 hom., cov: 33)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON2	NM_000305.3	c.74+1190G>A		intron_variant		ENST00000222572.8
PON2	NM_001018161.2	c.74+1190G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON2	ENST00000222572.8	c.74+1190G>A		intron_variant		1	NM_000305.3	P1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22160 AN: 152094 Hom.: 1925 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0495

Gnomad SAS AF: 0.0509

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.146 AC: 22184 AN: 152212 Hom.: 1927 Cov.: 33 AF XY: 0.142 AC XY: 10597 AN XY: 74420

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.0496

Gnomad4 SAS AF: 0.0512

Gnomad4 FIN AF: 0.0662

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.164

Alfa AF: 0.137 Hom.: 940

Bravo AF: 0.158

Asia WGS AF: 0.0710 AC: 248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.6
Dann	Benign	0.60

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: rs730365; hg19: chr7-95063000;