7-95406270-A-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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.226

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 (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_single_submitter, 1 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	UniProt
PON2	NM_000305.3	c.778-23T>A		intron_variant		ENST00000222572.8
LOC107986822	XR_007060439.1	n.557+9242A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PON2	ENST00000222572.8	c.778-23T>A		intron_variant		1	NM_000305.3	P1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42331 AN: 151944 Hom.: 6360 Cov.: 32

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

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.: 31 AF XY: 0.256 AC XY: 184918 AN XY: 721134

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.: 32 AF XY: 0.288 AC XY: 21399 AN XY: 74336

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	13
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

Other links and lift over

dbSNP: rs3735586; hg19: chr7-95035582; COSMIC: COSV56000847; COSMIC: COSV56000847;