chr7-95411684-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000305.3(PON2):c.463C>T(p.Leu155=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000512 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00053 ( 0 hom. )
Consequence
PON2
NM_000305.3 synonymous
NM_000305.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.89
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 Likely_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 7-95411684-G-A is Benign according to our data. Variant chr7-95411684-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3039135.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.89 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PON2 | NM_000305.3 | c.463C>T | p.Leu155= | synonymous_variant | 5/9 | ENST00000222572.8 | |
LOC107986822 | XR_007060439.1 | n.558-6632G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PON2 | ENST00000222572.8 | c.463C>T | p.Leu155= | synonymous_variant | 5/9 | 1 | NM_000305.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000289 AC: 44AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000275 AC: 69AN: 251180Hom.: 0 AF XY: 0.000258 AC XY: 35AN XY: 135754
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GnomAD4 exome AF: 0.000535 AC: 782AN: 1461694Hom.: 0 Cov.: 31 AF XY: 0.000531 AC XY: 386AN XY: 727140
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GnomAD4 genome AF: 0.000289 AC: 44AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74484
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PON2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 19, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
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Benign
DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at