rs11981433

Positions:

• chr7-95425028-T-C
• chr7-95425028-T-G

Variant summary

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

The NM_000305.3(PON2):​c.75-443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,940 control chromosomes in the GnomAD database, including 9,486 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 0.34 (9486 hom., cov: 32)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.815

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=-0.88).
• 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	UniProt
PON2	NM_000305.3	c.75-443A>G		intron_variant		ENST00000222572.8
PON2	NM_001018161.2	c.75-443A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON2	ENST00000222572.8	c.75-443A>G		intron_variant		1	NM_000305.3	P1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51110 AN: 151822 Hom.: 9487 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.00540

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.336 AC: 51123 AN: 151940 Hom.: 9486 Cov.: 32 AF XY: 0.325 AC XY: 24102 AN XY: 74268

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.00541

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.362

Alfa AF: 0.404 Hom.: 21350

Bravo AF: 0.332

Asia WGS AF: 0.116 AC: 409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.41
DANN	Benign	0.64

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: rs11981433; hg19: chr7-95054340;