rs201916690
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_201384.3(PLEC):c.8315G>A(p.Arg2772His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000067 in 1,612,854 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2772C) 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 -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.8315G>A | p.Arg2772His | missense_variant | 32/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.8273G>A | p.Arg2758His | missense_variant | 32/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.8315G>A | p.Arg2772His | missense_variant | 32/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.8273G>A | p.Arg2758His | missense_variant | 32/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000302 AC: 46AN: 152132Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000117 AC: 29AN: 247872Hom.: 0 AF XY: 0.0000965 AC XY: 13AN XY: 134744
GnomAD4 exome AF: 0.0000424 AC: 62AN: 1460722Hom.: 0 Cov.: 118 AF XY: 0.0000372 AC XY: 27AN XY: 726712
GnomAD4 genome ? AF: 0.000302 AC: 46AN: 152132Hom.: 0 Cov.: 34 AF XY: 0.000283 AC XY: 21AN XY: 74326
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 12, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 07, 2017 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 05, 2016 | - - |
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 28, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2799 of the PLEC protein (p.Arg2799His). This variant is present in population databases (rs201916690, gnomAD 0.08%). 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: 448078). 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. 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. - |
See cases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Jan 03, 2020 | ACMG classification criteria: PM2, BP1, BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at