ClinVar Genomic variation as it relates to human health
NM_001130987.2(DYSF):c.2864+1G>A
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001130987.2(DYSF):c.2864+1G>A
Variation ID: 443997 Accession: VCV000443997.15
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p13.2 2: 71568339 (GRCh38) [ NCBI UCSC ] 2: 71795469 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Oct 26, 2017 Feb 14, 2024 Nov 6, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001130987.2:c.2864+1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_003494.4:c.2810+1G>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_001130455.2:c.2813+1G>A splice donor NM_001130976.2:c.2768+1G>A splice donor NM_001130977.2:c.2768+1G>A splice donor NM_001130978.2:c.2810+1G>A splice donor NM_001130979.2:c.2903+1G>A splice donor NM_001130980.2:c.2861+1G>A splice donor NM_001130981.2:c.2861+1G>A splice donor NM_001130982.2:c.2906+1G>A splice donor NM_001130983.2:c.2813+1G>A splice donor NM_001130984.2:c.2771+1G>A splice donor NM_001130985.2:c.2864+1G>A splice donor NM_001130986.2:c.2771+1G>A splice donor NC_000002.12:g.71568339G>A NC_000002.11:g.71795469G>A NG_008694.1:g.119717G>A LRG_845:g.119717G>A LRG_845t1:c.2810+1G>A LRG_845t2:c.2864+1G>A - Protein change
- Other names
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- Canonical SPDI
- NC_000002.12:71568338:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- Variation affecting splicing function of RNA Variation Ontology [VariO:0397]
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Global minor allele
frequency (GMAF) HelpThe 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.
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0.00020 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
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 | ||
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HI score
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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. |
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DYSF | - | - |
GRCh38 GRCh37 |
4021 | 4070 |
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. |
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Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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May 3, 2020 | RCV000512137.6 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 6, 2023 | RCV001217776.7 | |
Pathogenic (2) |
criteria provided, single submitter
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Oct 6, 2023 | RCV001263253.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 10, 2022 | RCV002286745.2 |
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. |
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Pathogenic
(Oct 11, 2017)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2B
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
unknown
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Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV000607738.1
First in ClinVar: Oct 26, 2017 Last updated: Oct 26, 2017 |
Comment:
ACMG: +PVS1 +PM2 +PP3
Indication for testing: Muscle weakness. High CK. Biopsy with fat infiltration.
Sex: male
Method: WGS with Sanger verification of finding.
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Likely pathogenic
(Dec 22, 2017)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2B
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000796693.1
First in ClinVar: May 03, 2018 Last updated: May 03, 2018 |
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Pathogenic
(May 03, 2020)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2B
Affected status: yes
Allele origin:
unknown
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Genomic Research Center, Shahid Beheshti University of Medical Sciences
Accession: SCV000746544.2
First in ClinVar: Oct 26, 2017 Last updated: May 31, 2020 |
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Pathogenic
(Nov 06, 2023)
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criteria provided, single submitter
Method: clinical testing
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Qualitative or quantitative defects of dysferlin
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001389628.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects a donor splice site in intron 26 of the DYSF gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more)
This sequence change affects a donor splice site in intron 26 of the DYSF gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). This variant is present in population databases (rs199954546, gnomAD 0.002%). Disruption of this splice site has been observed in individual(s) with dysferlinopathy (PMID: 17994539, 18853459, 26000923). This variant is also known as IVS26+1G>A. ClinVar contains an entry for this variant (Variation ID: 443997). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV002577127.2
First in ClinVar: Oct 08, 2022 Last updated: Mar 04, 2023 |
Comment:
Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed … (more)
Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Identified in an individual with Miyoshi myopathy in published literature who also harbored a second DYSF variant in trans (Chakravorty et al., 2021); This variant is associated with the following publications: (PMID: 27602406, 31589614, 33610434, 33726816, 26000923, 22213072, Chakravorty2021[Preprint], 18853459) (less)
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Pathogenic
(Oct 06, 2023)
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criteria provided, single submitter
Method: clinical testing
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Miyoshi muscular dystrophy 1
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004194188.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Oct 23, 2020)
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no assertion criteria provided
Method: clinical testing
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Miyoshi muscular dystrophy 1
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Neuromuscular Department, Shariati Hospital, Tehran University of Medical Sciences
Accession: SCV001441253.1
First in ClinVar: Nov 06, 2020 Last updated: Nov 06, 2020 |
Comment:
Since age of 15, the patient developed bilateral foot plantar flexion weakness, difficulty climbing upstairs and some wasting of calf muscles. CK had been elevated … (more)
Since age of 15, the patient developed bilateral foot plantar flexion weakness, difficulty climbing upstairs and some wasting of calf muscles. CK had been elevated and the EMG was myopathic. (less)
Age: 20-29 years
Sex: female
Ethnicity/Population group: Iranian
Geographic origin: Iran
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Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Variation affecting splicing function of RNA
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Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV000607738.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Dysferlinopathy. | Adam MP | - | 2021 | PMID: 20301480 |
The Clinical Outcome Study for dysferlinopathy: An international multicenter study. | Harris E | Neurology. Genetics | 2016 | PMID: 27602406 |
Dysferlinopathy: mitochondrial abnormalities in human skeletal muscle. | Liu F | The International journal of neuroscience | 2016 | PMID: 26000923 |
Analysis of the DYSF mutational spectrum in a large cohort of patients. | Krahn M | Human mutation | 2009 | PMID: 18853459 |
Clinical, molecular, and protein correlations in a large sample of genetically diagnosed Italian limb girdle muscular dystrophy patients. | Guglieri M | Human mutation | 2008 | PMID: 17994539 |
Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes. | Nguyen K | Archives of neurology | 2007 | PMID: 17698709 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Text-mined citations for rs199954546 ...
HelpRecord last updated Feb 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.