20-37184251-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002951.5(RPN2):c.85C>T(p.Leu29Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000434 in 1,614,092 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 Uncertain significance (★).
Frequency
Consequence
NM_002951.5 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: 0.0000197 AC: 3AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000231 AC: 58AN: 251494Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135922
GnomAD4 exome AF: 0.0000458 AC: 67AN: 1461892Hom.: 0 Cov.: 32 AF XY: 0.0000440 AC XY: 32AN XY: 727248
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74346
ClinVar
Submissions by phenotype
Congenital disorder of glycosylation Uncertain:1
This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 29 of the RPN2 protein (p.Leu29Phe). This variant is present in population databases (rs771634062, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with RPN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2051509). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at