rs12704795

Positions:

• chr7-95424695-T-G

Variant summary

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

The ENST00000222572.8(PON2):​c.75-110A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 780,832 control chromosomes in the GnomAD database, including 54,955 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9481 hom., cov: 32)
  • Exomes 𝑓: 0.36 (45474 hom.)
• Consequence: PON2 ENST00000222572.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0850

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-95424695-T-G is Benign according to our data. Variant chr7-95424695-T-G is described in ClinVar as [Benign]. Clinvar id is 1259983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON2	NM_000305.3	c.75-110A>C		intron_variant		ENST00000222572.8	NP_000296.2
PON2	NM_001018161.2	c.75-110A>C		intron_variant			NP_001018171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8	c.75-110A>C		intron_variant		1	NM_000305.3	ENSP00000222572	P1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51097 AN: 151780 Hom.: 9482 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.00540

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.365

GnomAD4 exome AF: 0.361 AC: 226797 AN: 628934 Hom.: 45474 AF XY: 0.359 AC XY: 120411 AN XY: 335524

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.475

Gnomad4 EAS exome AF: 0.00331

Gnomad4 SAS exome AF: 0.254

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.420

Gnomad4 OTH exome AF: 0.363

GnomAD4 genome AF: 0.336 AC: 51110 AN: 151898 Hom.: 9481 Cov.: 32 AF XY: 0.325 AC XY: 24094 AN XY: 74230

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.00541

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.362

Alfa AF: 0.409 Hom.: 12684

Bravo AF: 0.332

Asia WGS AF: 0.116 AC: 408 AN: 3470

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.55

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: rs12704795; hg19: chr7-95054007;