rs12534274

Variant names:

• chr7-95428198-G-A
• rs12534274
• NM_000305.3:c.75-3613C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-95428198-G-A
• chr7-95428198-G-C
• chr7-95428198-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.75-3613C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,068 control chromosomes in the GnomAD database, including 6,313 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 0.28 (6313 hom., cov: 32)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON2	NM_000305.3	c.75-3613C>T		intron_variant	Intron 1 of 8	ENST00000222572.8	NP_000296.2
PON2	NM_001018161.2	c.75-3613C>T		intron_variant	Intron 1 of 8		NP_001018171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8	c.75-3613C>T		intron_variant	Intron 1 of 8	1	NM_000305.3	ENSP00000222572.3

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42472 AN: 151950 Hom.: 6303 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.280 AC: 42511 AN: 152068 Hom.: 6313 Cov.: 32 AF XY: 0.289 AC XY: 21493 AN XY: 74326

African (AFR) AF: 0.234 AC: 9688 AN: 41482

American (AMR) AF: 0.333 AC: 5092 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3470

East Asian (EAS) AF: 0.481 AC: 2487 AN: 5170

South Asian (SAS) AF: 0.370 AC: 1779 AN: 4810

European-Finnish (FIN) AF: 0.386 AC: 4074 AN: 10568

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17839 AN: 67970

Other (OTH) AF: 0.257 AC: 544 AN: 2114

Alfa AF: 0.262 Hom.: 15821

Bravo AF: 0.271

Asia WGS AF: 0.400 AC: 1390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.81
DANN	Benign	0.82
PhyloP100		-0.44
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: rs12534274; hg19: chr7-95057510;