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_213599.3(ANO5):c.148C>T (p.Arg50Ter)

CA379924765

468825 (ClinVar)

Gene: ANO5
Condition: autosomal recessive limb-girdle muscular dystrophy
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 6efeb5b0-da16-48e2-8a9c-b824a6aebdae
Approved on: 2025-01-07
Published on: 2025-01-07

HGVS expressions

NM_213599.3:c.148C>T
NM_213599.3(ANO5):c.148C>T (p.Arg50Ter)
NC_000011.10:g.22218255C>T
CM000673.2:g.22218255C>T
NC_000011.9:g.22239801C>T
CM000673.1:g.22239801C>T
NC_000011.8:g.22196377C>T
NG_015844.1:g.30080C>T
ENST00000682084.1:n.3322C>T
ENST00000682266.1:c.-270-2842C>T
ENST00000682341.1:c.139-2842C>T
ENST00000682530.1:c.136-488C>T
ENST00000682684.1:n.560-2842C>T
ENST00000683197.1:c.139-2842C>T
ENST00000683411.1:c.-270-2842C>T
ENST00000683437.1:c.-270-2842C>T
ENST00000683834.1:n.381-2842C>T
ENST00000683897.1:n.425-2842C>T
ENST00000684365.1:n.550-2842C>T
ENST00000684663.1:c.136-2842C>T
ENST00000324559.9:c.148C>T
ENST00000648804.1:n.670-331C>T
ENST00000324559.8:c.148C>T
NM_001142649.1:c.145C>T
NM_213599.2:c.148C>T
NM_001142649.2:c.145C>T
More

Pathogenic

Met criteria codes 4
PP4 PM2_Supporting PM3 PVS1
Not Met criteria codes 14
BP3 BP4 BP1 BP7 PS3 PS1 PP3 PP2 PM1 PM4 PM5 BA1 BS3 BS1

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 ANO5 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_213599.3: c.148C>T p.(Arg50Ter) variant in ANO5 is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 4/22 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 at least two individuals with LGMD, including confirmed in trans with a pathogenic or likely pathogenic variant (c.191dup, 1.0 pt, PMID: 23041008) (PM3). At least one patient with this variant displayed progressive limb girdle muscle weakness (PMID: 28403181; PP4). This variant is absent from gnomAD v3.1.2 and v2.1.1 (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; 01/07/2025): PVS1, PM3, PP4, PM2_Supporting.
Met criteria codes
PP4
At least one patient with this variant displayed progressive muscle weakness, which is highly specific for autosomal recessive limb-girdle muscular dystrophy (PP4, PMID:28403181).
PM2_Supporting
This variant is absent from gnomAD v3.1.2 and v2.1.1 (PM2_Supporting).
PM3
This variant has been detected in at least 2 individuals with autosomal recessive limb-girdle muscular dystrophy. Of those individuals, one was compound heterozygous for the variant and a pathogenic or likely pathogenic variant confirmed in trans by molecular methods (PM3, PMID: 23041008).
PVS1
The c.148C>T (p.Arg50Ter) variant in ANO5 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 4/22 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).
Not Met criteria codes
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
BP7
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
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
BA1
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
Curation History
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