7-95414538-T-G

Variant names:

• chr7-95414538-T-G
• rs1639
• NM_000305.3:c.201+1704A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000305.3(PON2):​c.201+1704A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,118 control chromosomes in the GnomAD database, including 3,865 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 0.19 (3865 hom., cov: 32)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 19 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 = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PON2	NM_000305.3	c.201+1704A>C		intron_variant	Intron 3 of 8	ENST00000222572.8	NP_000296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8	c.201+1704A>C		intron_variant	Intron 3 of 8	1	NM_000305.3	ENSP00000222572.3

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29029 AN: 152000 Hom.: 3861 Cov.: 32

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.191 AC: 29039 AN: 152118 Hom.: 3865 Cov.: 32 AF XY: 0.199 AC XY: 14769 AN XY: 74336

African (AFR) AF: 0.0659 AC: 2739 AN: 41534

American (AMR) AF: 0.344 AC: 5248 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 663 AN: 3468

East Asian (EAS) AF: 0.626 AC: 3233 AN: 5166

South Asian (SAS) AF: 0.276 AC: 1331 AN: 4820

European-Finnish (FIN) AF: 0.174 AC: 1836 AN: 10572

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13352 AN: 67972

Other (OTH) AF: 0.217 AC: 459 AN: 2112

Alfa AF: 0.208 Hom.: 6243

Bravo AF: 0.203

Asia WGS AF: 0.408 AC: 1417 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.76
PhyloP100		-0.13
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: rs1639; hg19: chr7-95043850;