NM_000117.3(EMD):c.188-6A>G AND X-linked Emery-Dreifuss muscular dystrophy

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Apr 12, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV001801337.6

Allele description [Variation Report for NM_000117.3(EMD):c.188-6A>G]

NM_000117.3(EMD):c.188-6A>G

Gene:

EMD:emerin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq28

Genomic location:

Preferred name:

NM_000117.3(EMD):c.188-6A>G

HGVS:

NC_000023.11:g.154379936A>G
NG_008677.1:g.10501A>G
NM_000117.3:c.188-6A>GMANE SELECT
LRG_745:g.10501A>G
NC_000023.10:g.153608296A>G

Links:

dbSNP: rs2148128297

NCBI 1000 Genomes Browser:

rs2148128297

Molecular consequence:

NM_000117.3:c.188-6A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: X-linked Emery-Dreifuss muscular dystrophy
Synonyms:: Muscular dystrophy, tardive Emery-Dreifuss type, with contractures
Identifiers:: MONDO: MONDO:0010680; MedGen: C0751337; Orphanet: 261; Orphanet: 98863

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002047550	Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	criteria provided, single submitter (Calame DG et al. (Ann Clin Transl Neurol 2021))	Pathogenic (Sep 15, 2021)	maternal	research	PubMed (1) [See all records that cite this PMID]
SCV003345335	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 12, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34524739, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002047550

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

criteria provided, single submitter

(Calame DG et al. (Ann Clin Transl Neurol 2021))

Pathogenic
(Sep 15, 2021)

maternal

research

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

SCV003345335

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 12, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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
not provided	maternal	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Deep clinicopathological phenotyping identifies a previously unrecognized pathogenic EMD splice variant.

Calame DG, Fatih JM, Herman I, Coban-Akdemir Z, Du H, Mitani T, Jhangiani SN, Marafi D, Gibbs RA, Posey JE, Mehta VP, Mohila CA, Abid F, Lotze TE, Pehlivan D, Adesina AM, Lupski JR.

Ann Clin Transl Neurol. 2021 Oct;8(10):2052-2058. doi: 10.1002/acn3.51454. Epub 2021 Sep 15.

PubMed [citation]

PMID:: 34524739
PMCID:: PMC8528454

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 Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine, SCV002047550.1

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003345335.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change falls in intron 2 of the EMD gene. It does not directly change the encoded amino acid sequence of the EMD protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Emery-Dreifuss muscular dystrophy (PMID: 34524739). ClinVar contains an entry for this variant (Variation ID: 1330306). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

#	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: Sep 29, 2024

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