chr7-95410236-G-A

Position:

• chr7-95410236-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000305.3(PON2):​c.495-135C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00785 in 739,628 control chromosomes in the GnomAD database, including 238 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.026 (178 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (60 hom.)
• Consequence: PON2 NM_000305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.944

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PON2	NM_000305.3	c.495-135C>T		intron_variant		ENST00000222572.8	NP_000296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PON2	ENST00000222572.8	c.495-135C>T		intron_variant		1	NM_000305.3	ENSP00000222572.3

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3962 AN: 152100 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.0911

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00845

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00314 AC: 1842 AN: 587410 Hom.: 60 AF XY: 0.00259 AC XY: 814 AN XY: 314754

Gnomad4 AFR exome AF: 0.0874

Gnomad4 AMR exome AF: 0.00559

Gnomad4 ASJ exome AF: 0.000693

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000152

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000286

Gnomad4 OTH exome AF: 0.00601

GnomAD4 genome AF: 0.0260 AC: 3962 AN: 152218 Hom.: 178 Cov.: 32 AF XY: 0.0240 AC XY: 1788 AN XY: 74414

Gnomad4 AFR AF: 0.0908

Gnomad4 AMR AF: 0.00844

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.0207 Hom.: 10

Bravo AF: 0.0295

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.50

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: rs17876148; hg19: chr7-95039548;