rs782316711
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_201384.3(PLEC):c.6845G>A(p.Arg2282Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,607,902 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2282W) 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.6845G>A | p.Arg2282Gln | missense_variant | 31/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.6803G>A | p.Arg2268Gln | missense_variant | 31/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.6845G>A | p.Arg2282Gln | missense_variant | 31/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.6803G>A | p.Arg2268Gln | missense_variant | 31/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152068Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000373 AC: 9AN: 241594Hom.: 0 AF XY: 0.0000378 AC XY: 5AN XY: 132424
GnomAD4 exome AF: 0.0000172 AC: 25AN: 1455834Hom.: 0 Cov.: 70 AF XY: 0.0000193 AC XY: 14AN XY: 724550
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152068Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74292
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 | May 08, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 2309 of the PLEC protein (p.Arg2309Gln). 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. 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. ClinVar contains an entry for this variant (Variation ID: 514859). This variant has not been reported in the literature in individuals affected with PLEC-related conditions. This variant is present in population databases (rs782316711, gnomAD 0.02%). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 15, 2017 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 22, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at