NM_003494.3(DYSF):c.2779del (p.Ala927Leufs) AND Qualitative or quantitative defects of dysferlin

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 24, 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:: RCV000546602.13

Allele description [Variation Report for NM_003494.3(DYSF):c.2779del (p.Ala927Leufs)]

NM_003494.3(DYSF):c.2779del (p.Ala927Leufs)

Gene:

DYSF:dysferlin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p13.2

Genomic location:

Preferred name:

NM_003494.3(DYSF):c.2779del (p.Ala927Leufs)

HGVS:

NC_000002.12:g.71568307del
NG_008694.1:g.119685del
NM_001130455.2:c.2782del
NM_001130976.2:c.2737del
NM_001130977.2:c.2737del
NM_001130978.2:c.2779del
NM_001130979.2:c.2872del
NM_001130980.2:c.2830del
NM_001130981.2:c.2830del
NM_001130982.2:c.2875del
NM_001130983.2:c.2782del
NM_001130984.2:c.2740del
NM_001130985.2:c.2833del
NM_001130986.2:c.2740del
NM_001130987.2:c.2833delMANE SELECT
NM_003494.4:c.2779del
NP_001123927.1:p.Ala928fs
NP_001124448.1:p.Ala913fs
NP_001124449.1:p.Ala913fs
NP_001124450.1:p.Ala927fs
NP_001124451.1:p.Ala958fs
NP_001124452.1:p.Ala944fs
NP_001124453.1:p.Ala944fs
NP_001124454.1:p.Ala959fs
NP_001124455.1:p.Ala928fs
NP_001124456.1:p.Ala914fs
NP_001124457.1:p.Ala945fs
NP_001124458.1:p.Ala914fs
NP_001124459.1:p.Ala945fs
NP_003485.1:p.Ala927fs
LRG_845t1:c.2779del
LRG_845t2:c.2833del
LRG_845:g.119685del
LRG_845p1:p.Ala927fs
LRG_845p2:p.Ala945fs
NC_000002.11:g.71795435del
NC_000002.11:g.71795437del
NM_003494.3:c.2779delG
NM_003494.4:c.2779delG

Note:

NCBI staff reviewed the sequence information reported in PubMed 17825554 Fig. 2 to determine the location of this allele on the current reference sequence.

Protein change:

A913fs

Links:

OMIM: 603009.0021; dbSNP: rs727503909

NCBI 1000 Genomes Browser:

rs727503909

Molecular consequence:

NM_001130455.2:c.2782del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130976.2:c.2737del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130977.2:c.2737del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130978.2:c.2779del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130979.2:c.2872del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130980.2:c.2830del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130981.2:c.2830del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130982.2:c.2875del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130983.2:c.2782del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130984.2:c.2740del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130985.2:c.2833del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130986.2:c.2740del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001130987.2:c.2833del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003494.4:c.2779del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Qualitative or quantitative defects of dysferlin
Synonyms:: Dysferlinopathy
Identifiers:: MONDO: MONDO:0016145; MedGen: C2931687

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000649638	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 24, 2023)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 17698709, 20301480, 16010686, 17825554, 18832576, 18853459, 19084402, 22194990, 25821721, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000649638

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 24, 2023)

germline

clinical testing

PubMed (10)
[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

Citations

PubMed

Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes.

Nguyen K, Bassez G, Krahn M, Bernard R, Laforêt P, Labelle V, Urtizberea JA, Figarella-Branger D, Romero N, Attarian S, Leturcq F, Pouget J, Lévy N, Eymard B.

Arch Neurol. 2007 Aug;64(8):1176-82.

PubMed [citation]

PMID:: 17698709

Dysferlinopathy.

Aoki M, Takahashi T.

2004 Feb 5 [updated 2021 May 27]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.

PubMed [citation]

PMID:: 20301480

See all PubMed Citations (10)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000649638.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

This sequence change creates a premature translational stop signal (p.Ala927Leufs*21) in the DYSF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). This variant is present in population databases (rs745407251, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with limb-girdle muscular dystrophy type 2B (LGMD2B), Miyoshi myopathy or pseudometabolic muscular dystrophy (PMID: 16010686, 17825554, 18832576, 18853459, 19084402, 22194990, 25821721). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6685). For these reasons, this variant has been classified as Pathogenic.

#	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: Oct 20, 2024

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