rs17876116

Positions:

• chr7-95418165-C-A
• chr7-95418165-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000305.3(PON2):​c.146-1868G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 152,268 control chromosomes in the GnomAD database, including 131 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 0.034 (131 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.034 (5179/152268) while in subpopulation AMR AF= 0.0485 (741/15292). AF 95% confidence interval is 0.0456. There are 131 homozygotes in gnomad4. There are 2545 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 131 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON2	NM_000305.3	c.146-1868G>T		intron_variant		ENST00000222572.8	NP_000296.2
PON2	NM_001018161.2	c.146-1868G>T		intron_variant			NP_001018171.1
PON2	XM_005250453.2	c.-33-1868G>T		intron_variant			XP_005250510.1
LOC107986822	XR_007060439.1	n.558-151C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8	c.146-1868G>T		intron_variant		1	NM_000305.3	ENSP00000222572.3

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 5181 AN: 152150 Hom.: 131 Cov.: 33

Gnomad AFR AF: 0.00970

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0463

Gnomad OTH AF: 0.0440

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0340 AC: 5179 AN: 152268 Hom.: 131 Cov.: 33 AF XY: 0.0342 AC XY: 2545 AN XY: 74456

Gnomad4 AFR AF: 0.00968

Gnomad4 AMR AF: 0.0485

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0155

Gnomad4 FIN AF: 0.0397

Gnomad4 NFE AF: 0.0464

Gnomad4 OTH AF: 0.0430

Alfa AF: 0.0439 Hom.: 174

Bravo AF: 0.0341

Asia WGS AF: 0.0100 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.32
DANN	Benign	0.48

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: rs17876116; hg19: chr7-95047477;