rs7493

chr7-95405463-G-Cchr7-95405463-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000305.3(PON2):c.932C>G(p.Ser311Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,611,536 control chromosomes in the GnomAD database, including 54,604 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (5893 hom., cov: 32)
  • Exomes 𝑓: 0.25 (48711 hom.)
• Consequence: PON2 NM_000305.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 9.26

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030953884).
• BP6: Variant 7-95405463-G-C is Benign according to our data. Variant chr7-95405463-G-C is described in ClinVar as [Benign]. Clinvar id is 7084.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PON2	NM_000305.3	c.932C>G	p.Ser311Cys	missense_variant	9/9	ENST00000222572.8
LOC107986822	XR_007060439.1	n.557+8435G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON2	ENST00000222572.8	c.932C>G	p.Ser311Cys	missense_variant	9/9	1	NM_000305.3	P1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40743 AN: 151836 Hom.: 5877 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.236

GnomAD3 exomes AF: 0.268 AC: 66761 AN: 249520 Hom.: 9608 AF XY: 0.274 AC XY: 36945 AN XY: 135036

Gnomad AFR exome AF: 0.296

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.174

Gnomad EAS exome AF: 0.189

Gnomad SAS exome AF: 0.363

Gnomad FIN exome AF: 0.434

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.253 AC: 368864 AN: 1459582 Hom.: 48711 Cov.: 33 AF XY: 0.257 AC XY: 186294 AN XY: 726236

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.426

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.268 AC: 40788 AN: 151954 Hom.: 5893 Cov.: 32 AF XY: 0.277 AC XY: 20602 AN XY: 74254

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.240

Alfa AF: 0.235 Hom.: 3321

Bravo AF: 0.246

TwinsUK AF: 0.241 AC: 894

ALSPAC AF: 0.245 AC: 944

ESP6500AA AF: 0.284 AC: 1250

ESP6500EA AF: 0.228 AC: 1961

ExAC AF: 0.271 AC: 32895

Asia WGS AF: 0.299 AC: 1040 AN: 3478

EpiCase AF: 0.230

EpiControl AF: 0.233

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

PARAOXONASE 2 POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jan 01, 1998

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

This variant is associated with the following publications: (PMID: 18759523, 21303902, 19930448, 19840942, 23225229, 19540141, 9443862) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.34
Cadd	Uncertain	24
Dann	Benign	0.96
Eigen	Benign	-0.11
Eigen_PC	Benign	0.020
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.59	T;T;.;T
MetaRNN	Benign	0.0031	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	0.00052	P;P;P
PrimateAI	Benign	0.46	T
Sift4G	Uncertain	0.052	T;T;T;T
Vest4		0.29
MPC		0.090
ClinPred		0.15	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7493; hg19: chr7-95034775; COSMIC: COSV56000788; COSMIC: COSV56000788;