rs368939666
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_201384.3(PLEC):c.7171G>A(p.Glu2391Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000715 in 1,608,424 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E2391G) has been classified as Uncertain significance.
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.7171G>A | p.Glu2391Lys | missense_variant | 31/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.7129G>A | p.Glu2377Lys | missense_variant | 31/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.7171G>A | p.Glu2391Lys | missense_variant | 31/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.7129G>A | p.Glu2377Lys | missense_variant | 31/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152152Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000253 AC: 6AN: 236796Hom.: 0 AF XY: 0.0000231 AC XY: 3AN XY: 129870
GnomAD4 exome AF: 0.0000728 AC: 106AN: 1456154Hom.: 0 Cov.: 70 AF XY: 0.0000621 AC XY: 45AN XY: 724376
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152270Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6AN XY: 74440
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 10, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 07, 2019 | - - |
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 | Oct 18, 2023 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2418 of the PLEC protein (p.Glu2418Lys). This variant is present in population databases (rs368939666, 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: 283100). 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. 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