rs10261470

Variant names:

• chr7-95432016-G-A
• rs10261470
• NM_000305.3:c.74+2862C>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.74+2862C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 151,330 control chromosomes in the GnomAD database, including 1,913 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 0.15 (1913 hom., cov: 32)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 11 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON2	NM_000305.3	c.74+2862C>T		intron_variant	Intron 1 of 8	ENST00000222572.8	NP_000296.2
PON2	NM_001018161.2	c.74+2862C>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.74+2862C>T		intron_variant	Intron 1 of 8	1	NM_000305.3	ENSP00000222572.3

Frequencies

GnomAD3 genomes AF: 0.145 AC: 21966 AN: 151236 Hom.: 1911 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0352

Gnomad SAS AF: 0.0407

Gnomad FIN AF: 0.0679

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.145 AC: 21989 AN: 151330 Hom.: 1913 Cov.: 32 AF XY: 0.142 AC XY: 10499 AN XY: 73882

African (AFR) AF: 0.223 AC: 9166 AN: 41140

American (AMR) AF: 0.134 AC: 2044 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 686 AN: 3466

East Asian (EAS) AF: 0.0353 AC: 181 AN: 5134

South Asian (SAS) AF: 0.0409 AC: 196 AN: 4788

European-Finnish (FIN) AF: 0.0679 AC: 702 AN: 10332

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.125 AC: 8496 AN: 67958

Other (OTH) AF: 0.164 AC: 342 AN: 2090

Alfa AF: 0.136 Hom.: 3189

Bravo AF: 0.157

Asia WGS AF: 0.0570 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.54
PhyloP100		-0.046
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: rs10261470; hg19: chr7-95061328;