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_000070.3(CAPN3):c.219del (p.Leu74fs)

CA2499222909

1072479 (ClinVar)

Gene: CAPN3 (HGNC:825)
Condition: autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152)
Inheritance Mode: Autosomal recessive inheritance
UUID: 2b7e9311-a423-41bc-bcfa-6db58a5cda0d
Approved on: 2025-01-07
Published on: 2025-01-07

HGVS expressions

NM_000070.3(CAPN3):c.219del (p.Leu74fs)
NM_000070.3:c.219del
NC_000015.10:g.42360024del
CM000677.2:g.42360024del
NC_000015.9:g.42652222del
CM000677.1:g.42652222del
NC_000015.8:g.40439514del
NG_008660.1:g.16922del
ENST00000349748.8:c.219del
ENST00000357568.8:c.219del
ENST00000397163.8:c.219del
ENST00000466369.5:n.540+5571del
ENST00000483208.5:n.540+5571del
ENST00000495723.1:n.540+5571del
ENST00000549793.5:n.540+5571del
ENST00000318023.11:c.219del
ENST00000349748.7:c.219del
ENST00000357568.7:c.219del
ENST00000397163.7:c.219del
NM_000070.2:c.219del
NM_024344.1:c.219del
NM_173087.1:c.219del
NM_024344.2:c.219del
NM_173087.2:c.219del
More

Likely Pathogenic

Met criteria codes 2
PVS1 PM2_Supporting
Not Met criteria codes 15
BS3 BS1 BP5 BP7 BP3 BP4 BP1 PS3 PS1 BA1 PP3 PP2 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 CAPN3 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_000070.3: c.219del p.(Leu74PhefsTer53) variant in CAPN3 is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 2/24 leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1). 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 Likely 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; 01/07/2025): PVS1, PM2_Supporting.
Met criteria codes
PVS1
The NM_000070.3:c.219del p.(Leu74PhefsTer53) variant in CAPN3 is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 2/24 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).
Not Met criteria codes
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
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
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
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
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
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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