rs10487133

Variant names:

• chr7-95406638-G-T
• rs10487133
• NM_000305.3:c.777+349C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000305.3(PON2):​c.777+349C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,192 control chromosomes in the GnomAD database, including 56,658 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 0.86 (56658 hom., cov: 32)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.746
• Publications: 10 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON2	NM_000305.3	c.777+349C>A		intron_variant	Intron 7 of 8	ENST00000222572.8	NP_000296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8	c.777+349C>A		intron_variant	Intron 7 of 8	1	NM_000305.3	ENSP00000222572.3

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131113 AN: 152074 Hom.: 56613 Cov.: 32

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.922

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.868

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

GnomAD4 genome AF: 0.862 AC: 131217 AN: 152192 Hom.: 56658 Cov.: 32 AF XY: 0.866 AC XY: 64428 AN XY: 74412

African (AFR) AF: 0.810 AC: 33611 AN: 41504

American (AMR) AF: 0.898 AC: 13747 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2972 AN: 3472

East Asian (EAS) AF: 0.839 AC: 4346 AN: 5182

South Asian (SAS) AF: 0.922 AC: 4447 AN: 4822

European-Finnish (FIN) AF: 0.901 AC: 9542 AN: 10592

Middle Eastern (MID) AF: 0.890 AC: 260 AN: 292

European-Non Finnish (NFE) AF: 0.877 AC: 59655 AN: 68006

Other (OTH) AF: 0.870 AC: 1835 AN: 2110

Alfa AF: 0.876 Hom.: 99137

Bravo AF: 0.857

Asia WGS AF: 0.863 AC: 3002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.77
PhyloP100		0.75
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: rs10487133; hg19: chr7-95035950;