ClinVar Miner

Submissions for variant NM_213599.3(ANO5):c.148C>T (p.Arg50Ter)

gnomAD frequency: 0.00001  dbSNP: rs1168346560
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Limb Girdle Muscular Dystrophy Variant Curation Expert Panel, ClinGen RCV005000183 SCV005620284 pathogenic Autosomal recessive limb-girdle muscular dystrophy 2025-01-07 reviewed by expert panel curation 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000545507 SCV000645874 pathogenic Gnathodiaphyseal dysplasia; Autosomal recessive limb-girdle muscular dystrophy type 2L 2019-10-29 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ANO5 are known to be pathogenic (PMID: 25891276, 23606453, 21186264). This variant has been reported in combination with another ANO5 variant in an individual affected with pseudo-metabolic myopathy (PMID: 23041008). ClinVar contains an entry for this variant (Variation ID: 468825). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg50*) in the ANO5 gene. It is expected to result in an absent or disrupted protein product.
Fulgent Genetics, Fulgent Genetics RCV000762829 SCV000893188 pathogenic Gnathodiaphyseal dysplasia; Autosomal recessive limb-girdle muscular dystrophy type 2L; Miyoshi muscular dystrophy 3 2018-10-31 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.