rs2286233

Positions:

• chr7-95424945-T-A
• chr7-95424945-T-C
• chr7-95424945-T-G

Variant summary

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

The ENST00000222572.8(PON2):​c.75-360A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 152,136 control chromosomes in the GnomAD database, including 55,296 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 0.85 (55296 hom., cov: 31)
• Consequence: PON2 ENST00000222572.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON2	NM_000305.3	c.75-360A>T		intron_variant		ENST00000222572.8	NP_000296.2
PON2	NM_001018161.2	c.75-360A>T		intron_variant			NP_001018171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8	c.75-360A>T		intron_variant		1	NM_000305.3	ENSP00000222572	P1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129345 AN: 152018 Hom.: 55250 Cov.: 31

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.878

Gnomad OTH AF: 0.854

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

GnomAD4 genome AF: 0.851 AC: 129448 AN: 152136 Hom.: 55296 Cov.: 31 AF XY: 0.856 AC XY: 63632 AN XY: 74374

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.899

Gnomad4 ASJ AF: 0.856

Gnomad4 EAS AF: 0.837

Gnomad4 SAS AF: 0.923

Gnomad4 FIN AF: 0.901

Gnomad4 NFE AF: 0.878

Gnomad4 OTH AF: 0.856

Alfa AF: 0.833 Hom.: 2621

Bravo AF: 0.848

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.1
DANN	Benign	0.52

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: rs2286233; hg19: chr7-95054257;