VCV000655612.2 - ClinVar

NM_001130987.2(DYSF):c.2566-1496_3203del

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001130987.2(DYSF):c.2566-1496_3203del

Variation ID: 655612 Accession: VCV000655612.2

Type and length

Deletion, 4,262 bp

Location

Cytogenetic: 2p13.2 2: 71566455-71570716 (GRCh38) [ NCBI UCSC ] 2: 71793585-71797846 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 16, 2020	Jul 16, 2020	Jan 29, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NM_001130987.2:c.2566-1496_3203del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice acceptor splice donor
NM_003494.4:c.2512-1496_3149del MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice acceptor splice donor
NM_001130455.2:c.2515-1496_3152del		splice acceptor splice donor
NM_001130976.2:c.2470-1496_3107del		splice acceptor splice donor
NM_001130977.2:c.2470-1496_3107del		splice acceptor splice donor
NM_001130978.2:c.2512-1496_3149del		splice acceptor splice donor
NM_001130979.2:c.2605-1496_3242del		splice acceptor splice donor
NM_001130980.2:c.2563-1496_3200del		splice acceptor splice donor
NM_001130981.2:c.2563-1496_3200del		splice acceptor splice donor
NM_001130982.2:c.2608-1496_3245del		splice acceptor splice donor
NM_001130983.2:c.2515-1496_3152del		splice acceptor splice donor
NM_001130984.2:c.2473-1496_3110del		splice acceptor splice donor
NM_001130985.2:c.2566-1496_3203del		splice acceptor splice donor
NM_001130986.2:c.2473-1496_3110del		splice acceptor splice donor
NC_000002.12:g.71566455_71570716del
NC_000002.11:g.71793585_71797846del
NG_008694.1:g.117833_122094del
LRG_845:g.117833_122094del
LRG_845t1:c.2512-1496_3149del
LRG_845t2:c.2566-1496_3203del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
DYSF		-	-	GRCh38 GRCh37	4063	4112

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Qualitative or quantitative defects of dysferlin	Pathogenic (1)	criteria provided, single submitter	Jan 29, 2019	RCV000811827.3

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jan 29, 2019)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Qualitative or quantitative defects of dysferlin Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000952114.2 First in ClinVar: Aug 14, 2019 Last updated: Jul 16, 2020	Publications: PubMed (5) PubMed: 17070050‚ 22194990‚ 19528035‚ 16934466‚ 14678801 Comment: This variant is a deletion of the genomic region encompassing exons 25-28 and part of exon 29 (c.2512-1496_3149del) of the DYSF gene. It is expected … (more) This variant is a deletion of the genomic region encompassing exons 25-28 and part of exon 29 (c.2512-1496_3149del) of the DYSF gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with DYSF-related conditions. This variant disrupts the p.Arg959 amino acid residue in DYSF. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 14678801, 22194990, 19528035, 16934466, 17070050), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. Loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). For these reasons, this variant has been classified as Pathogenic. (less)

Comment:

This variant is a deletion of the genomic region encompassing exons 25-28 and part of exon 29 (c.2512-1496_3149del) of the DYSF gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with DYSF-related conditions. This variant disrupts the p.Arg959 amino acid residue in DYSF. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 14678801, 22194990, 19528035, 16934466, 17070050), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. Loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). For these reasons, this variant has been classified as Pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Comparison of dysferlin expression in human skeletal muscle with that in monocytes for the diagnosis of dysferlin myopathy.	Gallardo E	PloS one	2011	PMID: 22194990
New aspects on patients affected by dysferlin deficient muscular dystrophy.	Klinge L	Journal of neurology, neurosurgery, and psychiatry	2010	PMID: 19528035
Dysferlin expression in monocytes: a source of mRNA for mutation analysis.	De Luna N	Neuromuscular disorders : NMD	2007	PMID: 17070050
Muscle protein analysis in the detection of heterozygotes for recessive limb girdle muscular dystrophy type 2B and 2E.	Fanin M	Neuromuscular disorders : NMD	2006	PMID: 16934466
Molecular analysis of LGMD-2B and MM patients: identification of novel DYSF mutations and possible founder effect in the Italian population.	Cagliani R	Neuromuscular disorders : NMD	2003	PMID: 14678801

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_001130987.2(DYSF):c.2566-1496_3203del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...