chr7-95410133-C-T

Position:

• chr7-95410133-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000305.3(PON2):​c.495-32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,544,858 control chromosomes in the GnomAD database, including 49,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5874 hom., cov: 32)
  • Exomes 𝑓: 0.25 (43555 hom.)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.82

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]

LOC107986822 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-95410133-C-T is Benign according to our data. Variant chr7-95410133-C-T is described in ClinVar as [Benign]. Clinvar id is 1259739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON2	NM_000305.3	c.495-32G>A		intron_variant		ENST00000222572.8	NP_000296.2
LOC107986822	XR_007060439.1	n.558-8183C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8	c.495-32G>A		intron_variant		1	NM_000305.3	ENSP00000222572	P1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40678 AN: 151920 Hom.: 5858 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.236

GnomAD3 exomes AF: 0.267 AC: 64417 AN: 241046 Hom.: 9092 AF XY: 0.274 AC XY: 35728 AN XY: 130598

Gnomad AFR exome AF: 0.294

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.175

Gnomad EAS exome AF: 0.189

Gnomad SAS exome AF: 0.363

Gnomad FIN exome AF: 0.433

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.250 AC: 348523 AN: 1392820 Hom.: 43555 Cov.: 24 AF XY: 0.254 AC XY: 177014 AN XY: 696272

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.360

Gnomad4 FIN exome AF: 0.423

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.268 AC: 40723 AN: 152038 Hom.: 5874 Cov.: 32 AF XY: 0.277 AC XY: 20594 AN XY: 74312

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.240

Alfa AF: 0.222 Hom.: 3980

Bravo AF: 0.246

Asia WGS AF: 0.300 AC: 1041 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs2286232; hg19: chr7-95039445;