VCV000282316.54 - ClinVar

NM_001130987.2(DYSF):c.342del (p.Ala116fs)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic/Likely pathogenic

5 out of 6 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001130987.2(DYSF):c.342del (p.Ala116fs)

Variation ID: 282316 Accession: VCV000282316.54

Type and length

Deletion, 1 bp

Location

Cytogenetic: 2p13.2 2: 71503316 (GRCh38) [ NCBI UCSC ] 2: 71730446 (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	Dec 6, 2016	Feb 15, 2026	Dec 16, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001130987.2:c.342del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001124459.1:p.Ala116fs	frameshift
NM_003494.4:c.339del MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003485.1:p.Ala115fs	frameshift
NM_001130455.2:c.342del	NP_001123927.1:p.Ala116fs	frameshift
NM_001130976.2:c.339del	NP_001124448.1:p.Ala115fs	frameshift
NM_001130977.2:c.339del	NP_001124449.1:p.Ala115fs	frameshift
NM_001130978.2:c.339del	NP_001124450.1:p.Ala115fs	frameshift
NM_001130979.2:c.339del	NP_001124451.1:p.Ala115fs	frameshift
NM_001130980.2:c.339del	NP_001124452.1:p.Ala115fs	frameshift
NM_001130981.2:c.339del	NP_001124453.1:p.Ala115fs	frameshift
NM_001130982.2:c.342del	NP_001124454.1:p.Ala116fs	frameshift
NM_001130983.2:c.342del	NP_001124455.1:p.Ala116fs	frameshift
NM_001130984.2:c.342del	NP_001124456.1:p.Ala116fs	frameshift
NM_001130985.2:c.342del	NP_001124457.1:p.Ala116fs	frameshift
NM_001130986.2:c.342del	NP_001124458.1:p.Ala116fs	frameshift
NM_003494.3:c.339del
NC_000002.12:g.71503316del
NC_000002.11:g.71730446del
NG_008694.1:g.54694del
LRG_845:g.54694del
LRG_845t1:c.339del	LRG_845p1:p.Ala115fs
LRG_845t2:c.342del	LRG_845p2:p.Ala116fs

... more HGVS ... less HGVS

Protein change

A115fs, A116fs

Other names

Canonical SPDI

NC_000002.12:71503315:A:

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.

Trans-Omics for Precision Medicine (TOPMed) 0.00000

Links

ClinGen: CA10604146 dbSNP: rs886042379 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	4560	4614

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.
not provided	Pathogenic (2)	criteria provided, multiple submitters, no conflicts	Oct 1, 2018	RCV000377821.38
Neuromuscular disease caused by qualitative or quantitative defects of dysferlin	Pathogenic (1)	criteria provided, single submitter	Dec 16, 2025	RCV000532444.10
Autosomal recessive limb-girdle muscular dystrophy type 2B	Likely pathogenic (1)	no assertion criteria provided	Apr 12, 2017	RCV000593550.4
Autosomal recessive limb-girdle muscular dystrophy type 2B Distal myopathy with anterior tibial onset Miyoshi muscular dystrophy 1	Likely pathogenic (1)	criteria provided, single submitter	May 12, 2022	RCV002502101.2
Miyoshi muscular dystrophy 1	Pathogenic (1)	criteria provided, single submitter	Mar 2, 2024	RCV003469224.2

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.	Expand all rows Collapse all rows 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.
Likely pathogenic (May 12, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Autosomal recessive limb-girdle muscular dystrophy type 2B Miyoshi muscular dystrophy 1 Distal myopathy with anterior tibial onset	Fulgent Genetics, Fulgent Genetics Accession: SCV002807596.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Pathogenic (Mar 02, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Miyoshi muscular dystrophy 1	Baylor Genetics Accession: SCV004192280.2 First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Pathogenic (Oct 01, 2018) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV001246778.36 First in ClinVar: May 12, 2020 Last updated: Jan 11, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 1

Pathogenic (Sep 14, 2015) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015)	not provided	Eurofins Ntd Llc (ga) Accession: SCV000333723.4 First in ClinVar: Dec 06, 2016 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DYSF Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 2 Zygosity: Homozygote, Single Heterozygote Sex: mixed

Pathogenic (Dec 16, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Neuromuscular disease caused by qualitative or quantitative defects of dysferlin	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000649660.8 First in ClinVar: Dec 26, 2017 Last updated: Feb 15, 2026	Publications: PubMed (3) PubMed: 17698709‚ 20301480‚ 27647186 Comment: show This sequence change creates a premature translational stop signal (p.Ala115Profs*36) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with dysferlinopathy (PMID: 27647186). ClinVar contains an entry for this variant (Variation ID: 282316). For these reasons, this variant has been classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely pathogenic (Apr 12, 2017) N Not contributing to aggregate classification	no assertion criteria provided	Autosomal recessive limb-girdle muscular dystrophy type 2B	Counsyl Accession: SCV000790869.3 First in ClinVar: Apr 02, 2018 Last updated: Jun 29, 2025	Publications: PubMed (1) PubMed: 27647186 Comment: show This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Comment:

This sequence change creates a premature translational stop signal (p.Ala115Profs*36) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with dysferlinopathy (PMID: 27647186). ClinVar contains an entry for this variant (Variation ID: 282316). For these reasons, this variant has been classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Dysferlinopathy.	Adam MP	-	2025	PMID: 20301480
Dysferlin Gene Mutation Spectrum in a Large Cohort of Chinese Patients with Dysferlinopathy.	Jin SQ	Chinese medical journal	2016	PMID: 27647186
Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes.	Nguyen K	Archives of neurology	2007	PMID: 17698709
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DYSF	-	-	-	-

Text-mined citations for rs886042379 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Feb 15, 2026