rs7803148

Positions:

• chr7-95418518-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.146-2221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,068 control chromosomes in the GnomAD database, including 8,564 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 0.31 (8564 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0380

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]

LOC107986822 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON2	NM_000305.3	c.146-2221G>A		intron_variant		ENST00000222572.8	NP_000296.2
LOC107986822	XR_007060439.1	n.760C>T		non_coding_transcript_exon_variant	2/2
PON2	NM_001018161.2	c.146-2221G>A		intron_variant			NP_001018171.1
PON2	XM_005250453.2	c.-33-2221G>A		intron_variant			XP_005250510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8	c.146-2221G>A		intron_variant		1	NM_000305.3	ENSP00000222572	P1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46765 AN: 151948 Hom.: 8565 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.00559

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.346

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.308 AC: 46762 AN: 152066 Hom.: 8564 Cov.: 32 AF XY: 0.297 AC XY: 22103 AN XY: 74336

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.00560

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.343

Alfa AF: 0.405 Hom.: 19955

Bravo AF: 0.300

Asia WGS AF: 0.106 AC: 372 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	3.0
DANN	Benign	0.23

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: rs7803148; hg19: chr7-95047830;