chr8-143932197-ATCT-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The ENST00000345136.8(PLEC):βc.2012_2014delβ(p.Lys671del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,612,212 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ). Synonymous variant affecting the same amino acid position (i.e. K671K) has been classified as Likely benign.
Frequency
Consequence
ENST00000345136.8 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLEC | NM_201378.4 | c.1970_1972del | p.Lys657del | inframe_deletion | 17/32 | ENST00000356346.7 | NP_958780.1 | |
PLEC | NM_201384.3 | c.2012_2014del | p.Lys671del | inframe_deletion | 17/32 | ENST00000345136.8 | NP_958786.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.2012_2014del | p.Lys671del | inframe_deletion | 17/32 | 1 | NM_201384.3 | ENSP00000344848 | ||
PLEC | ENST00000356346.7 | c.1970_1972del | p.Lys657del | inframe_deletion | 17/32 | 1 | NM_201378.4 | ENSP00000348702 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152050Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000206 AC: 5AN: 242146Hom.: 0 AF XY: 0.0000226 AC XY: 3AN XY: 132646
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1460044Hom.: 0 AF XY: 0.0000179 AC XY: 13AN XY: 726322
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74404
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 15, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 17, 2017 | A variant of uncertain significance has been identified in the PLEC gene. The c.2093_2095delAGA variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.2093_2095delAGA variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.2093_2095delAGA variant results in an in-frame deletion of one amino acid, denoted p.Lys698del. This variant occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. However, other in-frame deletions or missense variants have not been reported at nearby residues in the Human Gene Mutation Database (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
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 | Labcorp Genetics (formerly Invitae), Labcorp | Jan 15, 2024 | This variant, c.2093_2095del, results in the deletion of 1 amino acid(s) of the PLEC protein (p.Lys698del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs782157103, gnomAD 0.006%). 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: 450111). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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