ClinVar Genomic variation as it relates to human health
NM_001130987.2(DYSF):c.5139del (p.Phe1713fs)
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.5139del (p.Phe1713fs)
Variation ID: 374503 Accession: VCV000374503.34
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 2p13.2 2: 71664401 (GRCh38) [ NCBI UCSC ] 2: 71891531 (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 Apr 2, 2018 Apr 15, 2024 Jun 21, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001130987.2:c.5139del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001124459.1:p.Phe1713fs frameshift NM_003494.4:c.5022del MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003485.1:p.Phe1674fs frameshift NM_001130455.2:c.5025del NP_001123927.1:p.Phe1675fs frameshift NM_001130976.2:c.4980del NP_001124448.1:p.Phe1660fs frameshift NM_001130977.2:c.5043del NP_001124449.1:p.Phe1681fs frameshift NM_001130978.2:c.5085del NP_001124450.1:p.Phe1695fs frameshift NM_001130979.2:c.5115del NP_001124451.1:p.Phe1705fs frameshift NM_001130980.2:c.5073del NP_001124452.1:p.Phe1691fs frameshift NM_001130981.2:c.5136del NP_001124453.1:p.Phe1712fs frameshift NM_001130982.2:c.5118del NP_001124454.1:p.Phe1706fs frameshift NM_001130983.2:c.5088del NP_001124455.1:p.Phe1696fs frameshift NM_001130984.2:c.5046del NP_001124456.1:p.Phe1682fs frameshift NM_001130985.2:c.5076del NP_001124457.1:p.Phe1692fs frameshift NM_001130986.2:c.4983del NP_001124458.1:p.Phe1661fs frameshift NC_000002.12:g.71664403del NC_000002.11:g.71891533del NG_008694.1:g.215781del LRG_845:g.215781del LRG_845t1:c.5022del LRG_845p1:p.Phe1674fs LRG_845t2:c.5139del LRG_845p2:p.Phe1713fs - Protein change
- F1675fs, F1682fs, F1692fs, F1695fs, F1696fs, F1661fs, F1681fs, F1660fs, F1705fs, F1706fs, F1712fs, F1713fs, F1674fs, F1691fs
- Other names
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- Canonical SPDI
- NC_000002.12:71664400:TTT:TT
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
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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 |
4008 | 4057 |
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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Mar 12, 2018 | RCV000416117.25 | |
Pathogenic (1) |
no assertion criteria provided
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Feb 21, 2018 | RCV000984169.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Feb 1, 2023 | RCV001384057.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 21, 2023 | RCV003470372.1 |
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
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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
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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
(Mar 04, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000700992.2
First in ClinVar: Apr 02, 2018 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Pathogenic
(Mar 12, 2018)
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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: SCV000709976.2
First in ClinVar: Apr 02, 2018 Last updated: Dec 15, 2018 |
Comment:
The c.5022delT variant in the DYSF gene has been reported previously, using alternate nomenclature 5393delT, in an affected individual with limb-girdle muscular dystrophy 2B who … (more)
The c.5022delT variant in the DYSF gene has been reported previously, using alternate nomenclature 5393delT, in an affected individual with limb-girdle muscular dystrophy 2B who also harbored a DYSF nonsense variant, although it is unknown if parental studies were performed to determine the phase of these two variants (Walter et al., 2003). The c.5022delT has also been reported in an individual with Miyoshi myopathy who also harbored a DYSF missense variant, however, the phase of these variants is not known (Walter et al., 2013). The c.5022delT variant causes a frameshift starting with codon Phenylalanine 1674, changes this amino acid to a Leucine residue, and creates a premature Stop codon at position 48 of the new reading frame, denoted p.Phe1674LeufsX48. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.5022delT variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.5022delT as a pathogenic variant. (less)
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Pathogenic
(Jun 21, 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: SCV004196507.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Feb 01, 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: SCV001583429.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This premature translational stop signal has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 14673575). For these reasons, this variant has been classified as … (more)
This premature translational stop signal has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 14673575). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 374503). This variant is also known as 5393delT. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe1674Leufs*48) 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). (less)
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Likely pathogenic
(Nov 01, 2016)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV000493274.27
First in ClinVar: Jan 30, 2017 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(Feb 21, 2018)
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no assertion criteria provided
Method: clinical testing
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Autosomal recessive limb-girdle muscular dystrophy type 2B
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV001132182.1
First in ClinVar: Dec 23, 2019 Last updated: Dec 23, 2019 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Dysferlinopathy. | Adam MP | - | 2021 | PMID: 20301480 |
Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial. | Walter MC | Orphanet journal of rare diseases | 2013 | PMID: 23406536 |
Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes. | Nguyen K | Archives of neurology | 2007 | PMID: 17698709 |
Variable reduction of caveolin-3 in patients with LGMD2B/MM. | Walter MC | Journal of neurology | 2003 | PMID: 14673575 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DYSF | - | - | - | - |
Text-mined citations for rs1057519132 ...
HelpRecord last updated Apr 15, 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.