NM_182914.3(SYNE2):c.15446G>T (p.Arg5149Leu) AND Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 10, 2020
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:: RCV000694819.6

Allele description [Variation Report for NM_182914.3(SYNE2):c.15446G>T (p.Arg5149Leu)]

NM_182914.3(SYNE2):c.15446G>T (p.Arg5149Leu)

Gene:

SYNE2:spectrin repeat containing nuclear envelope protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q23.2

Genomic location:

Preferred name:

NM_182914.3(SYNE2):c.15446G>T (p.Arg5149Leu)

HGVS:

NC_000014.9:g.64143911G>T
NG_011756.2:g.387013G>T
NM_015180.6:c.15446G>T
NM_182914.3:c.15446G>TMANE SELECT
NP_055995.4:p.Arg5149Leu
NP_878918.2:p.Arg5149Leu
NP_878918.2:p.Arg5149Leu
LRG_872t1:c.15446G>T
LRG_872:g.387013G>T
LRG_872p1:p.Arg5149Leu
NC_000014.8:g.64610629G>T
NG_011756.1:g.295947G>T
NM_182914.2:c.15446G>T

Protein change:

R5149L

Links:

dbSNP: rs142206385

NCBI 1000 Genomes Browser:

rs142206385

Molecular consequence:

NM_015180.6:c.15446G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_182914.3:c.15446G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Emery-Dreifuss muscular dystrophy 5, autosomal dominant (EDMD5)
Synonyms:: EMERY-DREIFUSS MUSCULAR DYSTROPHY 5
Identifiers:: MONDO: MONDO:0013072; MedGen: C2751805; Orphanet: 261; OMIM: 612999

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000823281	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 10, 2020)	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

SCV000823281

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 10, 2020)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000823281.4

#	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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SYNE2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with leucine at codon 5149 of the SYNE2 protein (p.Arg5149Leu). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and leucine.

#	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: Feb 20, 2024

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