NM_201378.4(PLEC):c.5C>T (p.Ala2Val) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 19, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003805188.2

Allele description [Variation Report for NM_201378.4(PLEC):c.5C>T (p.Ala2Val)]

NM_201378.4(PLEC):c.5C>T (p.Ala2Val)

Gene:

PLEC:plectin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q24.3

Genomic location:

Preferred name:

NM_201378.4(PLEC):c.5C>T (p.Ala2Val)

HGVS:

NC_000008.11:g.143973468G>A
NG_012492.1:g.8278C>T
NG_115552.2:g.866G>A
NM_000445.5:c.193+1709C>T
NM_001410941.1:c.193+1709C>T
NM_201378.4:c.5C>T
NP_958780.1:p.Ala2Val
NC_000008.10:g.145047636G>A
NG_115552.1:g.866G>A

Protein change:

A2V

Molecular consequence:

NM_000445.5:c.193+1709C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001410941.1:c.193+1709C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_201378.4:c.5C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Epidermolysis bullosa simplex 5B, with muscular dystrophy (EBS5B)
Synonyms:: EPIDERMOLYSIS BULLOSA SIMPLEX AND LIMB-GIRDLE MUSCULAR DYSTROPHY; Epidermolysa bullosa simplex and limb girdle muscular dystrophy; Epidermolysis bullosa simplex with muscular dystrophy
Identifiers:: MONDO: MONDO:0009181; MedGen: C2931072; Orphanet: 257; OMIM: 226670

Name:: Epidermolysis bullosa simplex, Ogna type (EBS5A)
Synonyms:: EPIDERMOLYSIS BULLOSA SIMPLEX 5A, OGNA TYPE; Pidermolysis bullosa simplex 5A, Ogna type
Identifiers:: MONDO: MONDO:0007555; MedGen: C0432317; Orphanet: 79401; OMIM: 131950

Name:: Epidermolysis bullosa simplex 5C, with pyloric atresia (EBS5C)
Synonyms:: Epidermolysis bullosa simplex with pyloric atresia; PLEC1-Related Epidermolysis Bullosa with Pyloric Atresia
Identifiers:: MONDO: MONDO:0012807; MedGen: C2677349; Orphanet: 158684; OMIM: 612138

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2Q (LGMDR17)
Synonyms:: Limb-girdle muscular dystrophy, type 2Q; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 17
Identifiers:: MONDO: MONDO:0013390; MedGen: C3150989; Orphanet: 254361; OMIM: 613723

Name:: Epidermolysis bullosa simplex with nail dystrophy (EBS5D)
Identifiers:: MONDO: MONDO:0014661; MedGen: C4225309; OMIM: 616487

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004606879	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 19, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004606879

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 19, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004606879.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with PLEC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2 of the PLEC protein (p.Ala2Val). The PLEC gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_201378.3, and corresponds to NM_000445.4:c.193+1709C>T in the primary transcript.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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