rs17876116

Variant names:

• chr7-95418165-C-A
• rs17876116
• NM_000305.3:c.146-1868G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-95418165-C-A
• chr7-95418165-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000305.3(PON2):​c.146-1868G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.034 in 152,268 control chromosomes in the GnomAD database, including 131 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 0.034 (131 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855
• 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

ENSG00000233942 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.034 (5179/152268) while in subpopulation AMR AF = 0.0485 (741/15292). AF 95% confidence interval is 0.0456. There are 131 homozygotes in GnomAd4. There are 2545 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5179 AD gene.

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.146-1868G>T		intron	N/A	NP_000296.2	Q15165-2
	PON2	NM_001018161.2		c.146-1868G>T		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.146-1868G>T		intron	N/A	ENSP00000222572.3	Q15165-2
	PON2	ENST00000633192.1	TSL:1	c.209-1868G>T		intron	N/A	ENSP00000488378.1	A0A0J9YXF2
	PON2	ENST00000633531.1	TSL:1	c.146-1868G>T		intron	N/A	ENSP00000488838.1	Q15165-2

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 5181 AN: 152150 Hom.: 131 Cov.: 33

Gnomad AFR AF: 0.00970

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0463

Gnomad OTH AF: 0.0440

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0340 AC: 5179 AN: 152268 Hom.: 131 Cov.: 33 AF XY: 0.0342 AC XY: 2545 AN XY: 74456

African (AFR) AF: 0.00968 AC: 402 AN: 41546

American (AMR) AF: 0.0485 AC: 741 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.0155 AC: 75 AN: 4828

European-Finnish (FIN) AF: 0.0397 AC: 421 AN: 10614

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0464 AC: 3153 AN: 68022

Other (OTH) AF: 0.0430 AC: 91 AN: 2114

Alfa AF: 0.0431 Hom.: 218

Bravo AF: 0.0341

Asia WGS AF: 0.0100 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.32
DANN	Benign	0.48
PhyloP100		-0.85
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: rs17876116; hg19: chr7-95047477;