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.2503_2505del (p.Phe835del)

CA242118

195634 (ClinVar)

Gene: ANO5
Condition: autosomal recessive limb-girdle muscular dystrophy
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 66985fba-19e3-49da-a0e9-4d02471dcc58
Approved on: 2025-01-07
Published on: 2025-01-07

HGVS expressions

NM_213599.3:c.2503_2505del
NM_213599.3(ANO5):c.2503_2505del (p.Phe835del)
NC_000011.10:g.22276182_22276184del
CM000673.2:g.22276182_22276184del
NC_000011.9:g.22297728_22297730del
CM000673.1:g.22297728_22297730del
NC_000011.8:g.22254304_22254306del
NG_015844.1:g.88007_88009del
ENST00000532043.2:n.520_522del
ENST00000682266.1:c.2053_2055del
ENST00000682341.1:c.2461_2463del
ENST00000683197.1:c.2372+1435_2372+1437del
ENST00000683411.1:c.2053_2055del
ENST00000683437.1:c.2053_2055del
ENST00000683613.1:n.3497_3499del
ENST00000684663.1:c.2458_2460del
ENST00000324559.9:c.2503_2505del
ENST00000648804.1:n.2838_2840del
ENST00000324559.8:c.2503_2505del
ENST00000532043.1:n.520_522del
NM_001142649.1:c.2500_2502del
NM_213599.2:c.2503_2505del
NM_001142649.2:c.2500_2502del
More

Likely Pathogenic

Met criteria codes 4
PM4 PM3_Strong PP4 PM2_Supporting
Not Met criteria codes 22
PM1 PM5 PM6 BA1 BS2 BS4 BS3 BS1 BP5 BP7 BP2 BP4 BP1 BP3 PVS1 PS4 PS2 PS3 PS1 PP1 PP3 PP2

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.2503_2505del variant in ANO5 is predicted to cause a change in the length of the protein due to an in-frame deletion of one amino acid in a non-repeat region, p.(Phe835del) (PM4). This variant has been detected with a pathogenic ANO5 variant in at least four individuals with LGMD, including confirmed in trans in one patient (c.191dup, 1 pt, ClinVar SCV000767093.6 internal data communication) and in unknown phase in two patients (c.2018A>G p.(Tyr673Cys), 0.5 pts, ClinVar SCV000767093.6 internal data communication; c.191dup, 0.5 pts, ClinVar SCV000574876.19 internal data communication) (PM3_Strong). At least one patient with this variant displayed progressive limb girdle muscle weakness (PP4). The filtering allele frequency of this variant is 0.000017531 (the upper threshold of the 95% CI of 12/1109046 exome chromosomes) in the European (non-Finnish) population in gnomAD v4.1.0, which is less than the ClinGen LGMD threshold ≤0.0001 for PM2_Supporting, meeting this criterion (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): PM4, PM3_Strong, PP4, PM2_Supporting.
Met criteria codes
PM4
The c.2503_2505del variant is predicted to cause a change in the length of the protein (p.Phe835del) due to an in-frame deletion of 1 amino acid in a non-repeat region (PM4).
PM3_Strong
This variant has been detected with a pathogenic ANO5 variant in at least four individuals with LGMD, including confirmed in trans in one patient (c.191dup, 1 pt, SCV000767093.6) and in unknown phase in two patients (c.2018A>G p.(Tyr673Cys), 0.5 pts, ClinVar SCV000767093.6 internal data communication; c.191dup, 0.5 pts, ClinVar SCV000574876.19 internal data communication) (PM3_Strong).
PP4
At least one patient with this variant displayed progressive weakness, which is specific for LGMD 2L (PP4_Supporting, internal laboratory data).
PM2_Supporting
The filtering allele frequency of this variant is 0.000017531 (the upper threshold of the 95% CI of 12/1109046 exome chromosomes) in the European (non-Finnish) population in gnomAD v4.1.0, which is less than the ClinGen LGMD threshold ≤0.0001 for PM2_Supporting, meeting this criterion (PM2_Supporting).
Not Met criteria codes
PM1
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
PM6
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
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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
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
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
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
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
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
Curation History
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