rs62641756
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_201384.3(PLEC):c.6757G>A(p.Ala2253Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000821 in 1,602,544 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2253V) has been classified as Uncertain significance.
Frequency
Consequence
NM_201384.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEC | NM_201384.3 | c.6757G>A | p.Ala2253Thr | missense_variant | 31/32 | ENST00000345136.8 | |
PLEC | NM_201378.4 | c.6715G>A | p.Ala2239Thr | missense_variant | 31/32 | ENST00000356346.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEC | ENST00000345136.8 | c.6757G>A | p.Ala2253Thr | missense_variant | 31/32 | 1 | NM_201384.3 | ||
PLEC | ENST00000356346.7 | c.6715G>A | p.Ala2239Thr | missense_variant | 31/32 | 1 | NM_201378.4 |
Frequencies
GnomAD3 genomes ? AF: 0.00373 AC: 567AN: 152166Hom.: 2 Cov.: 33
GnomAD3 exomes AF: 0.00103 AC: 249AN: 241050Hom.: 1 AF XY: 0.000834 AC XY: 110AN XY: 131900
GnomAD4 exome AF: 0.000513 AC: 744AN: 1450260Hom.: 7 Cov.: 71 AF XY: 0.000465 AC XY: 336AN XY: 722010
GnomAD4 genome ? AF: 0.00375 AC: 571AN: 152284Hom.: 3 Cov.: 33 AF XY: 0.00373 AC XY: 278AN XY: 74454
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 21, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 15, 2015 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | PLEC: BP4, BS1, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 26, 2021 | - - |
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 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at