Submissions for variant NM_213599.3(ANO5):c.616A>G (p.Thr206Ala)

gnomAD frequency: 0.00922  dbSNP: rs78266558

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Limb Girdle Muscular Dystrophy Variant Curation Expert Panel, ClinGen	RCV004998234	SCV005620273	benign	Autosomal recessive limb-girdle muscular dystrophy	2025-01-07	reviewed by expert panel	curation	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.
Eurofins Ntd Llc (ga)	RCV000116355	SCV000338846	benign	not specified	2016-01-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000116355	SCV000525088	benign	not specified	2016-05-06	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000551276	SCV000645920	benign	Gnathodiaphyseal dysplasia; Autosomal recessive limb-girdle muscular dystrophy type 2L	2025-02-03	criteria provided, single submitter	clinical testing
Mendelics	RCV000988502	SCV001138249	benign	Gnathodiaphyseal dysplasia	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001103563	SCV001260336	benign	ANO5-Related Muscle Diseases	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Athena Diagnostics	RCV000116355	SCV001475529	benign	not specified	2020-01-22	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000988502	SCV002539189	benign	Gnathodiaphyseal dysplasia	2021-12-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002259605	SCV002539190	benign	Miyoshi muscular dystrophy 3	2021-12-05	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002259604	SCV002539191	benign	Autosomal recessive limb-girdle muscular dystrophy type 2L	2021-12-05	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002505038	SCV002794799	likely benign	Gnathodiaphyseal dysplasia; Autosomal recessive limb-girdle muscular dystrophy type 2L; Miyoshi muscular dystrophy 3	2022-02-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003390801	SCV004129938	benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	ANO5: BP4, BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV003390801	SCV005317826	benign	not provided		criteria provided, single submitter	not provided
Genetic Services Laboratory, University of Chicago	RCV000116355	SCV000150278	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
PreventionGenetics, part of Exact Sciences	RCV004542837	SCV004773906	benign	ANO5-related disorder	2020-10-12	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).