Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001130987.2(DYSF):c.5977G>T (p.Glu1993Ter)

CA347226407

2674990 (ClinVar)

Gene: DYSF (HGNC:8291)
Condition: autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152)
Inheritance Mode: Autosomal recessive inheritance
UUID: 18d31a5f-ea98-4ab2-80fc-927245377ba8
Approved on: 2025-01-08
Published on: 2025-01-08

HGVS expressions

NM_001130987.2(DYSF):c.5977G>T (p.Glu1993Ter)
NM_001130987.2:c.5977G>T
NC_000002.12:g.71679149G>T
CM000664.2:g.71679149G>T
NC_000002.11:g.71906279G>T
CM000664.1:g.71906279G>T
NC_000002.10:g.71759787G>T
NG_008694.1:g.230527G>T
ENST00000698057.1:c.3391G>T
ENST00000698058.1:c.2608G>T
ENST00000698059.1:c.2716G>T
ENST00000258104.8:c.5860G>T
ENST00000410020.8:c.5977G>T
ENST00000258104.7:c.5860G>T
ENST00000394120.6:c.5863G>T
ENST00000409366.5:c.5926G>T
ENST00000409582.7:c.5974G>T
ENST00000409651.5:c.5956G>T
ENST00000409744.5:c.5884G>T
ENST00000409762.5:c.5911G>T
ENST00000410020.7:c.5977G>T
ENST00000410041.1:c.5914G>T
ENST00000413539.6:c.5953G>T
ENST00000429174.6:c.5923G>T
ENST00000479049.6:n.2745G>T
NM_001130455.1:c.5863G>T
NM_001130976.1:c.5818G>T
NM_001130977.1:c.5881G>T
NM_001130978.1:c.5923G>T
NM_001130979.1:c.5953G>T
NM_001130980.1:c.5911G>T
NM_001130981.1:c.5974G>T
NM_001130982.1:c.5956G>T
NM_001130983.1:c.5926G>T
NM_001130984.1:c.5884G>T
NM_001130985.1:c.5914G>T
NM_001130986.1:c.5821G>T
NM_001130987.1:c.5977G>T
NM_003494.3:c.5860G>T
NM_001130455.2:c.5863G>T
NM_001130976.2:c.5818G>T
NM_001130977.2:c.5881G>T
NM_001130978.2:c.5923G>T
NM_001130979.2:c.5953G>T
NM_001130980.2:c.5911G>T
NM_001130981.2:c.5974G>T
NM_001130982.2:c.5956G>T
NM_001130983.2:c.5926G>T
NM_001130984.2:c.5884G>T
NM_001130985.2:c.5914G>T
NM_001130986.2:c.5821G>T
NM_003494.4:c.5860G>T
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Pathogenic

Met criteria codes 4
PP4_Strong PM3 PVS1 PM2_Supporting

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Limb Girdle Muscular Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for DYSF Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Limb Girdle Muscular Dystrophy VCEP
The NM_003494.4: c.5860G>T p.(Glu1954Ter) variant in DYSF, which is also known as NM_001130987.2: c.5977G>T p.(Glu1993Ter), is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 52/55, leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1). This variant has been confirmed in trans with a pathogenic variant in an individual with LGMD (c.857T>A (p.Val286Glu), 1.0 pt, PMID: 33927379) (PM3). This individual displayed progressive limb-girdle muscle weakness and absent dysferlin protein expression, which is highly specific for DYSF-associated LGMD (PP4_Strong). This variant is absent from gnomAD v2.1.1 and v3.1.2 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 1.0.0; 01/08/2025): PVS1, PM3, PP4_Strong, PM2_Supporting.
Met criteria codes
PP4_Strong
At least one patient with this variant displayed progressive limb-girdle muscle weakness and absent dysferlin protein expression, which is highly specific for DYSF-associated LGMD (PP4_Strong, PMID: 33927379).
PM3
This variant has been confirmed in trans with a pathogenic variant in an individual with LGMD (c.857T>A (p.Val286Glu), 1.0 pt, PMID: 33927379) (PM3).
PVS1
The NM_003494.4: c.5860G>T p.(Glu1954Ter) variant in DYSF, which is also known as NM_001130987.2: c.5977G>T p.(Glu1993Ter), is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 52/55, leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1).
PM2_Supporting
This variant is absent from gnomAD v2.1.1 and v3.1.2 (PM2_Supporting).
Curation History
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