Variant: NM_213599.3(ANO5):c.2236-21_2236-17del

CA5923496

1634480 (ClinVar)

Gene: ANO5

Condition: autosomal recessive limb-girdle muscular dystrophy

Inheritance Mode: Autosomal recessive inheritance

UUID: 2f20ec3a-ac77-4fc5-997f-47222c96defb

Approved on: 2025-01-09

Published on: 2025-01-09

HGVS expressions

NM_213599.3:c.2236-21_2236-17del
NM_213599.3(ANO5):c.2236-21_2236-17del
NC_000011.10:g.22274548_22274552del
CM000673.2:g.22274548_22274552del
NC_000011.9:g.22296094_22296098del
CM000673.1:g.22296094_22296098del
NC_000011.8:g.22252670_22252674del
NG_015844.1:g.86373_86377del
ENST00000532043.2:n.253-21_253-17del
ENST00000682266.1:c.1786-21_1786-17del
ENST00000682341.1:c.2194-21_2194-17del
ENST00000683197.1:c.2194-21_2194-17del
ENST00000683411.1:c.1786-21_1786-17del
ENST00000683437.1:c.1786-21_1786-17del
ENST00000683613.1:n.3230-21_3230-17del
ENST00000684663.1:c.2191-21_2191-17del
ENST00000324559.9:c.2236-21_2236-17del
ENST00000648804.1:n.2571-21_2571-17del
ENST00000324559.8:c.2236-21_2236-17del
ENST00000532043.1:n.253-21_253-17del
NM_001142649.1:c.2233-21_2233-17del
NM_213599.2:c.2236-21_2236-17del
NM_001142649.2:c.2233-21_2233-17del

Likely Benign

• Met criteria codes: BP4 BS1

• Not Met criteria codes: BP7

Expert Panel

Limb Girdle Muscular Dystrophy VCEP

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

Evidence submitted by expert panel

Limb Girdle Muscular Dystrophy VCEP

The NM_213599.3: c.2236-21_2236-17del variant in ANO5 is an intronic deletion. The filtering allele frequency for this variant is 0.001514 for the African/African American population in gnomAD v4.1.0 (the lower threshold of the 95% CI of 59/31020 exome chromosomes), which is greater than the ClinGen LGMD VCEP threshold of 0.001 for BS1, and therefore meets this criterion (BS1). The SpliceAI prediction score for this variant is 0, which is less than the VCEP threshold of 0.05 (BP4). Because this variant occurs in a splice region (+7/-21), BP7 is not applicable. In summary, this variant meets the criteria to be classified as Likely Benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the LGMD VCEP (LGMD VCEP specifications version 1.0.0; 01/09/2025): BS1, BP4.

Met criteria codes

• BP4: The SpliceAI prediction score for this variant is 0, which is greater than the LGMD threshold of 0.10 for this criterion (BP4).
• BS1: The filtering allele frequency for this variant is 0.001514 for the African/African American population in gnomAD v4.1.0 (the lower threshold of the 95% CI of 59/31020 exome chromosomes), which is greater than the ClinGen LGMD VCEP threshold of 0.001 for BS1, and therefore meets this criterion (BS1).

Not Met criteria codes

• BP7: While the SpliceAI score of 0 is less than the LGMD VCEP threshold of 0.10, this variant occurs in a splice region (+7/-21) and so BP7 is not applicable.