rs201301042

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000305.3(PON2):​c.832G>T​(p.Asp278Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PON2
NM_000305.3 missense

Scores

9
7
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.07
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.937

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PON2NM_000305.3 linkc.832G>T p.Asp278Tyr missense_variant Exon 8 of 9 ENST00000222572.8 NP_000296.2 Q15165-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PON2ENST00000222572.8 linkc.832G>T p.Asp278Tyr missense_variant Exon 8 of 9 1 NM_000305.3 ENSP00000222572.3 Q15165-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460328
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726604
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.48
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.71
D;.;D;.
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.98
D;D;.;D
M_CAP
Benign
0.054
D
MetaRNN
Pathogenic
0.94
D;D;D;D
MetaSVM
Benign
-0.34
T
MutationAssessor
Uncertain
2.9
M;.;M;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Pathogenic
-8.1
.;D;D;.
REVEL
Uncertain
0.51
Sift
Pathogenic
0.0
.;D;D;.
Sift4G
Uncertain
0.0030
D;D;D;D
Polyphen
1.0
D;.;D;.
Vest4
0.97
MutPred
0.75
Loss of disorder (P = 0.0758);.;Loss of disorder (P = 0.0758);.;
MVP
0.57
MPC
0.54
ClinPred
1.0
D
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.95
gMVP
0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-95035505; API