rs2375005

Positions:

• chr7-95407564-T-A
• chr7-95407564-T-C
• chr7-95407564-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.696-496A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,002 control chromosomes in the GnomAD database, including 22,493 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 0.53 (22493 hom., cov: 33)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON2	NM_000305.3	c.696-496A>T		intron_variant		ENST00000222572.8
LOC107986822	XR_007060439.1	n.557+10536T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON2	ENST00000222572.8	c.696-496A>T		intron_variant		1	NM_000305.3	P1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81208 AN: 151884 Hom.: 22457 Cov.: 33

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.535 AC: 81304 AN: 152002 Hom.: 22493 Cov.: 33 AF XY: 0.549 AC XY: 40770 AN XY: 74292

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.512

Alfa AF: 0.481 Hom.: 2451

Bravo AF: 0.535

Asia WGS AF: 0.753 AC: 2615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.21

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: rs2375005; hg19: chr7-95036876;