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.616A>G (p.Thr206Ala)

CA151833

128391 (ClinVar)

Gene: ANO5
Condition: autosomal recessive limb-girdle muscular dystrophy
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 42f6b694-71d5-4e8d-97ac-32d6eac162b9
Approved on: 2025-01-07
Published on: 2025-01-07

HGVS expressions

NM_213599.3:c.616A>G
NM_213599.3(ANO5):c.616A>G (p.Thr206Ala)
NC_000011.10:g.22227554A>G
CM000673.2:g.22227554A>G
NC_000011.9:g.22249100A>G
CM000673.1:g.22249100A>G
NC_000011.8:g.22205676A>G
NG_015844.1:g.39379A>G
ENST00000682266.1:c.166A>G
ENST00000682341.1:c.574A>G
ENST00000682530.1:c.*548A>G
ENST00000682684.1:n.995A>G
ENST00000683197.1:c.574A>G
ENST00000683411.1:c.166A>G
ENST00000683437.1:c.166A>G
ENST00000683613.1:n.1610A>G
ENST00000683834.1:n.816A>G
ENST00000684663.1:c.571A>G
ENST00000324559.9:c.616A>G
ENST00000648804.1:n.1181A>G
ENST00000324559.8:c.616A>G
NM_001142649.1:c.613A>G
NM_213599.2:c.616A>G
NM_001142649.2:c.613A>G
More

Benign

Met criteria codes 1
BA1
Not Met criteria codes 25
BS2 BS4 BS3 BS1 BP5 BP7 BP2 BP4 BP1 BP3 PS2 PS4 PS3 PS1 PP4 PP1 PP3 PP2 PVS1 PM6 PM2 PM3 PM1 PM5 PM4

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.616A>G variant in ANO5 is a missense variant predicted to cause substitution of threonine by alanine at amino acid 206 (p.Thr206Ala). The filtering allele frequency of this variant is 0.02707 (the lower threshold of the 95% CI of 562/250584 African/African American chromosomes in gnomAD v2.1.1), which is higher than the ClinGen LGMD VCEP threshold (>0.003) for BA1 and therefore meets this criterion (BA1). At least one patient who displayed progressive weakness and a possible congenital myopathy has been reported to have this variant (PMID: 25891276); however, PP4 is not applied when BA1 is met. In summary, this variant meets the criteria to be classified as Benign 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): BA1.
Met criteria codes
BA1
The filtering allele frequency (the lower threshold of the 95% CI of 562/250584) of the c.616A>G (p.Thr206Ala) variant in ANO5 is 0.02707 for African/African American chromosomes by gnomAD v2.1.1, which is higher than the ClinGen LGMD VCEP threshold (>0.002) for BA1, and therefore meets this criterion (BA1).
Not Met criteria codes
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
The computational predictor REVEL gives a score of 0.16, which is neither above nor below the thresholds predicting a damaging or benign impact on ANO5 function (≥0.70 and ≤0.10, respectively).
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
PS2
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
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
PP4
At least one patient with this variant displayed progressive weakness and a possible congenital myopathy (PMID: 25891276). However, PP4 is not applicable when BA1 is met.
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
PVS1
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
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
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
PM5
NM_213599.3(ANO5):c.617C>G (p.Thr206Ser) = VUS
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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