rs2375005

Variant names:

• chr7-95407564-T-A
• rs2375005
• NM_000305.3:c.696-496A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-95407564-T-A
• chr7-95407564-T-C
• chr7-95407564-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.97).
• 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 rank	MANE	Protein	UniProt
PON2	NM_000305.3	c.696-496A>T		intron_variant	Intron 6 of 8	ENST00000222572.8	NP_000296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8	c.696-496A>T		intron_variant	Intron 6 of 8	1	NM_000305.3	ENSP00000222572.3

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

African (AFR) AF: 0.578 AC: 23960 AN: 41446

American (AMR) AF: 0.617 AC: 9423 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1328 AN: 3468

East Asian (EAS) AF: 0.833 AC: 4308 AN: 5174

South Asian (SAS) AF: 0.689 AC: 3316 AN: 4816

European-Finnish (FIN) AF: 0.629 AC: 6646 AN: 10560

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30648 AN: 67950

Other (OTH) AF: 0.512 AC: 1083 AN: 2114

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
PhyloP100		0.36
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: rs2375005; hg19: chr7-95036876;