7-95406141-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000305.3(PON2):c.884C>T(p.Pro295Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,613,584 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Consequence
NM_000305.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152090Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251354Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135850
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461494Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727052
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152090Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74270
ClinVar
Submissions by phenotype
not provided Uncertain:1
The PON2 p.Pro295Leu variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs771860411) and in Cosmic (FATHMM predicted pathogenic; score=0.98). The variant was identified in 6 of 251354 chromosomes at a frequency of 0.000024 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 5 of 113696 chromosomes (freq: 0.000044) and Latino in 1 of 34570 chromosomes (freq: 0.000029); it was not observed in the African, Ashkenazi Jewish, East Asian, European (Finnish), Other and South Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Pro295 residue is not conserved in mammals however 4 of 5 computational analyses (PolyPhen-2, SIFT, BLOSUM, MutationTaster) suggest that the variant may impact the protein. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at