rs200880699
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_201384.3(PLEC):c.7192C>T(p.Arg2398Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00011 in 1,610,920 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. R2398H) has been classified as Uncertain significance.
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.7192C>T | p.Arg2398Cys | missense_variant | 31/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.7150C>T | p.Arg2384Cys | missense_variant | 31/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.7192C>T | p.Arg2398Cys | missense_variant | 31/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.7150C>T | p.Arg2384Cys | missense_variant | 31/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000467 AC: 71AN: 152088Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000157 AC: 38AN: 242722Hom.: 0 AF XY: 0.000143 AC XY: 19AN XY: 132642
GnomAD4 exome AF: 0.0000727 AC: 106AN: 1458714Hom.: 0 Cov.: 70 AF XY: 0.0000579 AC XY: 42AN XY: 725702
GnomAD4 genome ? AF: 0.000466 AC: 71AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.000511 AC XY: 38AN XY: 74400
ClinVar
Submissions by phenotype
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 | Dec 23, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 2425 of the PLEC protein (p.Arg2425Cys). This variant is present in population databases (rs200880699, gnomAD 0.2%). 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: 285988). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 14, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at