rs2299263

chr7-95411099-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.494+554G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 151,940 control chromosomes in the GnomAD database, including 5,865 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 0.27 (5865 hom., cov: 32)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON2	NM_000305.3	c.494+554G>A		intron_variant		ENST00000222572.8
LOC107986822	XR_007060439.1	n.558-7217C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON2	ENST00000222572.8	c.494+554G>A		intron_variant		1	NM_000305.3	P1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40652 AN: 151820 Hom.: 5848 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.268 AC: 40699 AN: 151940 Hom.: 5865 Cov.: 32 AF XY: 0.277 AC XY: 20567 AN XY: 74238

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.449

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.239

Alfa AF: 0.249 Hom.: 1368

Bravo AF: 0.246

Asia WGS AF: 0.300 AC: 1041 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	4.0
Dann	Benign	0.34

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: rs2299263; hg19: chr7-95040411;