rs12534274

Positions:

• chr7-95428198-G-A
• chr7-95428198-G-C
• chr7-95428198-G-T

Variant summary

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

The NM_000305.3(PON2):​c.75-3613C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,068 control chromosomes in the GnomAD database, including 6,313 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 0.28 (6313 hom., cov: 32)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON2	NM_000305.3	c.75-3613C>T		intron_variant		ENST00000222572.8
PON2	NM_001018161.2	c.75-3613C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON2	ENST00000222572.8	c.75-3613C>T		intron_variant		1	NM_000305.3	P1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42472 AN: 151950 Hom.: 6303 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.280 AC: 42511 AN: 152068 Hom.: 6313 Cov.: 32 AF XY: 0.289 AC XY: 21493 AN XY: 74326

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.257

Alfa AF: 0.256 Hom.: 5595

Bravo AF: 0.271

Asia WGS AF: 0.400 AC: 1390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.81
DANN	Benign	0.82

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: rs12534274; hg19: chr7-95057510;