rs782581787
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting
The NM_201384.3(PLEC):c.5390G>A(p.Arg1797His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000228 in 1,538,656 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1797C) has been classified as Likely benign.
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.5390G>A | p.Arg1797His | missense_variant | 31/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.5348G>A | p.Arg1783His | missense_variant | 31/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.5390G>A | p.Arg1797His | missense_variant | 31/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.5348G>A | p.Arg1783His | missense_variant | 31/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 151666Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000150 AC: 21AN: 140078Hom.: 0 AF XY: 0.000167 AC XY: 13AN XY: 77818
GnomAD4 exome AF: 0.000234 AC: 325AN: 1386990Hom.: 0 Cov.: 68 AF XY: 0.000235 AC XY: 161AN XY: 685168
GnomAD4 genome AF: 0.000171 AC: 26AN: 151666Hom.: 0 Cov.: 34 AF XY: 0.000162 AC XY: 12AN XY: 74020
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 29, 2018 | The R1824H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R1824H variant is observed in 17/68,386 (0.03%) alleles from individuals of European background (Lek et al., 2016). This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In addition, most reported pathogenic variants in the PLEC gene are truncating/loss-of-function. However, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 14, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 13, 2021 | - - |
Epidermolysis bullosa simplex, Ogna type;C2677349:Epidermolysis bullosa simplex 5C, with pyloric atresia;C2931072:Epidermolysis bullosa simplex 5B, with muscular dystrophy;C3150989:Autosomal recessive limb-girdle muscular dystrophy type 2Q;C4225309:Epidermolysis bullosa simplex with nail dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1824 of the PLEC protein (p.Arg1824His). This variant is present in population databases (rs782581787, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PLEC-related conditions. ClinVar contains an entry for this variant (Variation ID: 196720). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PLEC protein function with a negative predictive value of 80%. 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. - |
Arrhythmogenic right ventricular dysplasia 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at