NM_000305.3:c.885G>A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate
The NM_000305.3(PON2):c.885G>A(p.Pro295Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,628 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 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152124Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251350Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135844
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461504Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 727052
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152124Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74306
ClinVar
Submissions by phenotype
not provided Benign:1
Variant summary: The PON2 c.885G>A (p.Pro295Pro) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 4/120854 control chromosomes at a frequency of 0.0000331, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic PON2 variant (0.00002), suggesting this variant is likely a benign polymorphism. However, the small number of carriers in ExAC does not allow for unequivocally classification as Benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at