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.757C>T (p.Gln253Ter)

CA10606688

290209 (ClinVar)

Gene: DYSF (HGNC:8291)
Condition: autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152)
Inheritance Mode: Autosomal recessive inheritance
UUID: 963bc9b6-9fb1-45c8-b949-286d31b48168
Approved on: 2025-01-08
Published on: 2025-01-08

HGVS expressions

NM_001130987.2:c.757C>T
NM_001130987.2(DYSF):c.757C>T (p.Gln253Ter)
NC_000002.12:g.71513919C>T
CM000664.2:g.71513919C>T
NC_000002.11:g.71741049C>T
CM000664.1:g.71741049C>T
NC_000002.10:g.71594557C>T
NG_008694.1:g.65297C>T
ENST00000258104.8:c.661C>T
ENST00000410020.8:c.757C>T
ENST00000258104.7:c.661C>T
ENST00000394120.6:c.664C>T
ENST00000409366.5:c.664C>T
ENST00000409582.7:c.754C>T
ENST00000409651.5:c.757C>T
ENST00000409744.5:c.664C>T
ENST00000409762.5:c.754C>T
ENST00000410020.7:c.757C>T
ENST00000410041.1:c.757C>T
ENST00000413539.6:c.754C>T
ENST00000429174.6:c.661C>T
NM_001130455.1:c.664C>T
NM_001130976.1:c.661C>T
NM_001130977.1:c.661C>T
NM_001130978.1:c.661C>T
NM_001130979.1:c.754C>T
NM_001130980.1:c.754C>T
NM_001130981.1:c.754C>T
NM_001130982.1:c.757C>T
NM_001130983.1:c.664C>T
NM_001130984.1:c.664C>T
NM_001130985.1:c.757C>T
NM_001130986.1:c.664C>T
NM_001130987.1:c.757C>T
NM_003494.3:c.661C>T
NM_001130455.2:c.664C>T
NM_001130976.2:c.661C>T
NM_001130977.2:c.661C>T
NM_001130978.2:c.661C>T
NM_001130979.2:c.754C>T
NM_001130980.2:c.754C>T
NM_001130981.2:c.754C>T
NM_001130982.2:c.757C>T
NM_001130983.2:c.664C>T
NM_001130984.2:c.664C>T
NM_001130985.2:c.757C>T
NM_001130986.2:c.664C>T
NM_003494.4:c.661C>T
More

Pathogenic

Met criteria codes 4
PM2_Supporting PVS1 PP4 PM3
Not Met criteria codes 22
BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP4 BP1 PS4 PS2 PS3 PS1 BA1 PP1 PP3 PP2 PM6 PM1 PM4 PM5

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.661C>T p.(Gln221Ter) variant in DYSF, which is also known as NM_001130987.2: c.757C>T p.(Gln253Ter), is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 6/55, leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1). This variant has been detected in a homozygous state in two patients with LGMD (1.0 pt, ClinVar SCV003309109.1 internal data communication, PMID: 30564623, Jain Foundation Dysferlin Registry internal data communication) (PM3, PP4). 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, PM2_Supporting, PM3, PP4.
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v2.1.1 and v.3.1.2 (PM2_Supporting).
PVS1
The NM_003494.4: 661C>T (p.Gln221Ter) variant in DYSF is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 6/55 leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1).
PP4
At least one patient with this variant displayed a progressive limb girdle pattern of muscle weakness (PP4; ClinVar SCV003309109.1).
PM3
This variant has been detected in a homozygous state in two individuals (1.0 pt; ClinVar SCV003309109.1, PMID: 30564623; Jain Foundation Dysferlin Registry) (PM3).
Not Met criteria codes
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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