Variant 7-95406270-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000305.3(PON2):c.778-23T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,600,014 control chromosomes in the GnomAD database, including 54,720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6380 hom., cov: 32)

Exomes 𝑓: 0.25 ( 48340 hom. )

Consequence

PON2
NM_000305.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.226

Variant links:

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 links:

LOC107986822 (HGNC:):

LOC107986822 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-95406270-A-T is Benign according to our data. Variant chr7-95406270-A-T is described in ClinVar as [Benign]. Clinvar id is 1231210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON2	NM_000305.3 linkuse as main transcript	c.778-23T>A		intron_variant		ENST00000222572.8	NP_000296.2
LOC107986822	XR_007060439.1 linkuse as main transcript	n.557+9242A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8 linkuse as main transcript	c.778-23T>A		intron_variant		1	NM_000305.3	ENSP00000222572	P1	Q15165-2

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42331

AN:

151944

Hom.:

6360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.372

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.191

Gnomad SAS

AF:

0.365

Gnomad FIN

AF:

0.450

Gnomad MID

AF:

0.252

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.244

GnomAD3 exomes

AF:

0.270

AC:

67637

AN:

250670

Hom.:

9810

AF XY:

0.275

AC XY:

37304

AN XY:

135550

show subpopulations

Gnomad AFR exome

AF:

0.328

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.176

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:

0.252

GnomAD4 exome

AF:

0.253

AC:

365854

AN:

1447952

Hom.:

48340

Cov.:

AF XY:

0.256

AC XY:

184918

AN XY:

721134

show subpopulations

Gnomad4 AFR exome

AF:

0.334

Gnomad4 AMR exome

AF:

0.216

Gnomad4 ASJ exome

AF:

0.179

Gnomad4 EAS exome

AF:

0.197

Gnomad4 SAS exome

AF:

0.362

Gnomad4 FIN exome

AF:

0.426

Gnomad4 NFE exome

AF:

0.238

Gnomad4 OTH exome

AF:

0.255

GnomAD4 genome

AF:

0.279

AC:

42386

AN:

152062

Hom.:

6380

Cov.:

AF XY:

0.288

AC XY:

21399

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.322

Gnomad4 AMR

AF:

0.226

Gnomad4 ASJ

AF:

0.186

Gnomad4 EAS

AF:

0.191

Gnomad4 SAS

AF:

0.365

Gnomad4 FIN

AF:

0.450

Gnomad4 NFE

AF:

0.243

Gnomad4 OTH

AF:

0.249

Alfa

AF:

0.251

Hom.:

979

Bravo

AF:

0.258

Asia WGS

AF:

0.303

AC:

1054

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

-0.82

CADD

Benign

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over