rs17876193

Positions:

• chr7-95422338-G-C
• chr7-95422338-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.145+2177C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.07 in 152,248 control chromosomes in the GnomAD database, including 505 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 0.070 (505 hom., cov: 33)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON2	NM_000305.3	c.145+2177C>G		intron_variant		ENST00000222572.8	NP_000296.2
LOC107986822	XR_007060439.1	n.4580G>C		non_coding_transcript_exon_variant	2/2
PON2	NM_001018161.2	c.145+2177C>G		intron_variant			NP_001018171.1
PON2	XM_005250453.2	c.-34+2177C>G		intron_variant			XP_005250510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8	c.145+2177C>G		intron_variant		1	NM_000305.3	ENSP00000222572	P1

Frequencies

GnomAD3 genomes AF: 0.0701 AC: 10667 AN: 152128 Hom.: 506 Cov.: 33

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.0839

Gnomad FIN AF: 0.0630

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0921

Gnomad OTH AF: 0.0762

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

GnomAD4 genome AF: 0.0700 AC: 10661 AN: 152248 Hom.: 505 Cov.: 33 AF XY: 0.0696 AC XY: 5185 AN XY: 74444

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.0710

Gnomad4 ASJ AF: 0.0899

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.0840

Gnomad4 FIN AF: 0.0630

Gnomad4 NFE AF: 0.0921

Gnomad4 OTH AF: 0.0768

Alfa AF: 0.0759 Hom.: 78

Bravo AF: 0.0711

Asia WGS AF: 0.127 AC: 439 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.65

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: rs17876193; hg19: chr7-95051650;