7-95409980-AAAC-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PM4_SupportingBP6_Moderate
The NM_000305.3(PON2):c.613_615delGTT(p.Val205del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000142 in 1,613,786 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Consequence
NM_000305.3 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152144Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000330 AC: 83AN: 251304Hom.: 1 AF XY: 0.000309 AC XY: 42AN XY: 135816
GnomAD4 exome AF: 0.000145 AC: 212AN: 1461642Hom.: 1 AF XY: 0.000166 AC XY: 121AN XY: 727120
GnomAD4 genome AF: 0.000112 AC: 17AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74314
ClinVar
Submissions by phenotype
not specified Benign:1
Variant summary: PON2 c.613_615delGTT (p.Val205del) results in an in-frame deletion that is predicted to remove one of the two valine residues in codon 204-205. The variant allele was found at a frequency of 0.0003 in 276976 control chromosomes, predominantly at a frequency of 0.0068 within the Ashkenazi Jewish subpopulation in the gnomAD database, including one homozygote. The observed variant frequency is approximately 15 fold of the estimated maximal expected allele frequency for a pathogenic variant in PON2 causing Early Onset Coronary Artery Disease phenotype (2e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.613_615delGTT in individuals affected with Early Onset Coronary Artery Disease and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. 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