7-95406126-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate
The NM_000305.3(PON2):c.899C>T(p.Ser300Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,474 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
Consequence
NM_000305.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152138Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251250Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135802
GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461336Hom.: 0 Cov.: 31 AF XY: 0.0000468 AC XY: 34AN XY: 726976
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152138Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74314
ClinVar
Submissions by phenotype
not specified Benign:1
Variant summary: PON2 c.899C>T (p.Ser300Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 251250 control chromosomes. The observed variant frequency is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in PON2 causing Early Onset Coronary Artery Disease phenotype (2e-05). To our knowledge, no occurrence of c.899C>T in individuals affected with Early Onset Coronary Artery Disease and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at