chr7-95411691-C-T
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_000305.3(PON2):c.456G>A(p.Leu152=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000831 in 1,613,930 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0042 ( 7 hom., cov: 32)
Exomes 𝑓: 0.00048 ( 7 hom. )
Consequence
PON2
NM_000305.3 synonymous
NM_000305.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0690
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 Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 7-95411691-C-T is Benign according to our data. Variant chr7-95411691-C-T is described in ClinVar as [Benign]. Clinvar id is 714350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.069 with no splicing effect.
BS2
?
High Homozygotes in GnomAd at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PON2 | NM_000305.3 | c.456G>A | p.Leu152= | synonymous_variant | 5/9 | ENST00000222572.8 | |
LOC107986822 | XR_007060439.1 | n.558-6625C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PON2 | ENST00000222572.8 | c.456G>A | p.Leu152= | synonymous_variant | 5/9 | 1 | NM_000305.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00417 AC: 634AN: 152132Hom.: 6 Cov.: 32
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GnomAD3 exomes AF: 0.00110 AC: 275AN: 251140Hom.: 4 AF XY: 0.000678 AC XY: 92AN XY: 135740
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GnomAD4 exome AF: 0.000478 AC: 698AN: 1461680Hom.: 7 Cov.: 31 AF XY: 0.000382 AC XY: 278AN XY: 727144
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GnomAD4 genome ? AF: 0.00422 AC: 643AN: 152250Hom.: 7 Cov.: 32 AF XY: 0.00419 AC XY: 312AN XY: 74442
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 10, 2022 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 23, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at