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NM_001130987.2(DYSF):c.951+3_951+4del AND Autosomal recessive limb-girdle muscular dystrophy type 2B

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 3, 2018
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:
RCV001005020.4

Allele description [Variation Report for NM_001130987.2(DYSF):c.951+3_951+4del]

NM_001130987.2(DYSF):c.951+3_951+4del

Gene:
DYSF:dysferlin [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2p13.2
Genomic location:
Preferred name:
NM_001130987.2(DYSF):c.951+3_951+4del
HGVS:
  • NC_000002.12:g.71516245_71516246del
  • NG_008694.1:g.67623_67624del
  • NM_001130455.2:c.858+3_858+4del
  • NM_001130976.2:c.855+3_855+4del
  • NM_001130977.2:c.855+3_855+4del
  • NM_001130978.2:c.855+3_855+4del
  • NM_001130979.2:c.948+3_948+4del
  • NM_001130980.2:c.948+3_948+4del
  • NM_001130981.2:c.948+3_948+4del
  • NM_001130982.2:c.951+3_951+4del
  • NM_001130983.2:c.858+3_858+4del
  • NM_001130984.2:c.858+3_858+4del
  • NM_001130985.2:c.951+3_951+4del
  • NM_001130986.2:c.858+3_858+4del
  • NM_001130987.2:c.951+3_951+4delMANE SELECT
  • NM_003494.4:c.855+3_855+4del
  • LRG_845t1:c.855+3_855+4del
  • LRG_845t2:c.951+3_951+4del
  • LRG_845:g.67623_67624del
  • NC_000002.11:g.71743374_71743375delTA
  • NC_000002.11:g.71743375_71743376del
Links:
dbSNP: rs1573663867
NCBI 1000 Genomes Browser:
rs1573663867
Molecular consequence:
  • NM_001130455.2:c.858+3_858+4del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001130976.2:c.855+3_855+4del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001130977.2:c.855+3_855+4del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001130978.2:c.855+3_855+4del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001130979.2:c.948+3_948+4del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001130980.2:c.948+3_948+4del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001130981.2:c.948+3_948+4del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001130982.2:c.951+3_951+4del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001130983.2:c.858+3_858+4del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001130984.2:c.858+3_858+4del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001130985.2:c.951+3_951+4del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001130986.2:c.858+3_858+4del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001130987.2:c.951+3_951+4del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_003494.4:c.855+3_855+4del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Autosomal recessive limb-girdle muscular dystrophy type 2B (LGMDR2)
Synonyms:
Limb-girdle muscular dystrophy, type 2B; Muscular dystrophy, limb-girdle, type 3; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 2
Identifiers:
MONDO: MONDO:0009676; MedGen: C1850889; Orphanet: 268; OMIM: 253601

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001164585Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Dec 3, 2018) 		germlineresearch

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedresearch

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001164585.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)

Description

The heterozygous c.951+3_951+4delAT variant in DYSF was identified by our study in the compound heterozygous state, with a VUS, in two siblings with limb-girdle muscular dystrophy (LGMD). This variant was absent from large population studies. This variant is located in the 5’ splice region. Computational tools do suggest an impact to splicing (destruction of a natural splice site and creation of an in-frame cryptic splice site) and another variant predicted to impact the same splicing site was reported pathogenic in ClinVar (Variation ID: 283267). However, this information is not predictive enough to determine pathogenicity. Loss of function of the DYSF gene is an established disease mechanism for autosomal recessive LGMD. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PVS1_Moderate, PP1 (Richards 2015).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024