Variant 7-95405509-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.907-21T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,605,186 control chromosomes in the GnomAD database, including 43,090 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3616 hom., cov: 32)

Exomes 𝑓: 0.21 ( 39474 hom. )

Consequence

PON2
NM_000305.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.77

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 7-95405509-A-T is Benign according to our data. Variant chr7-95405509-A-T is described in ClinVar as [Benign]. Clinvar id is 1237156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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/exons	MANE	Protein	UniProt
PON2	NM_000305.3 linkuse as main transcript	c.907-21T>A		intron_variant		ENST00000222572.8	NP_000296.2
LOC107986822	XR_007060439.1 linkuse as main transcript	n.557+8481A>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.907-21T>A		intron_variant		1	NM_000305.3	ENSP00000222572	P1	Q15165-2

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27852

AN:

152044

Hom.:

3613

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0634

Gnomad AMI

AF:

0.139

Gnomad AMR

AF:

0.334

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.626

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.201

GnomAD3 exomes

AF:

0.253

AC:

62976

AN:

248664

Hom.:

10856

AF XY:

0.247

AC XY:

33312

AN XY:

134610

show subpopulations

Gnomad AFR exome

AF:

0.0592

Gnomad AMR exome

AF:

0.434

Gnomad ASJ exome

AF:

0.165

Gnomad EAS exome

AF:

0.635

Gnomad SAS exome

AF:

0.262

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.188

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.212

AC:

308256

AN:

1453024

Hom.:

39474

Cov.:

AF XY:

0.212

AC XY:

153287

AN XY:

723344

show subpopulations

Gnomad4 AFR exome

AF:

0.0521

Gnomad4 AMR exome

AF:

0.418

Gnomad4 ASJ exome

AF:

0.166

Gnomad4 EAS exome

AF:

0.668

Gnomad4 SAS exome

AF:

0.255

Gnomad4 FIN exome

AF:

0.154

Gnomad4 NFE exome

AF:

0.193

Gnomad4 OTH exome

AF:

0.213

GnomAD4 genome

AF:

0.183

AC:

27860

AN:

152162

Hom.:

3616

Cov.:

AF XY:

0.191

AC XY:

14182

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0632

Gnomad4 AMR

AF:

0.335

Gnomad4 ASJ

AF:

0.172

Gnomad4 EAS

AF:

0.626

Gnomad4 SAS

AF:

0.274

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.188

Gnomad4 OTH

AF:

0.203

Alfa

AF:

0.172

Hom.:

535

Bravo

AF:

0.195

Asia WGS

AF:

0.405

AC:

1407

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 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.55

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

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