rs17876193

Variant names:

• chr7-95422338-G-C
• rs17876193
• NM_000305.3:c.145+2177C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-95422338-G-C
• chr7-95422338-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

PON2 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC107986822 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000305.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PON2	NM_000305.3	MANE Select	c.145+2177C>G		intron	N/A	NP_000296.2	Q15165-2
	PON2	NM_001018161.2		c.145+2177C>G		intron	N/A	NP_001018171.1	Q15165-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PON2	ENST00000222572.8	TSL:1 MANE Select	c.145+2177C>G		intron	N/A	ENSP00000222572.3	Q15165-2
	PON2	ENST00000633192.1	TSL:1	c.208+2177C>G		intron	N/A	ENSP00000488378.1	A0A0J9YXF2
	PON2	ENST00000633531.1	TSL:1	c.145+2177C>G		intron	N/A	ENSP00000488838.1	Q15165-2

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

African (AFR) AF: 0.0173 AC: 721 AN: 41564

American (AMR) AF: 0.0710 AC: 1087 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0899 AC: 312 AN: 3472

East Asian (EAS) AF: 0.196 AC: 1010 AN: 5166

South Asian (SAS) AF: 0.0840 AC: 405 AN: 4822

European-Finnish (FIN) AF: 0.0630 AC: 668 AN: 10598

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0921 AC: 6263 AN: 68002

Other (OTH) AF: 0.0768 AC: 162 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.65
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17876193; hg19: chr7-95051650;