Submissions for variant NM_213599.3(ANO5):c.155A>G (p.Asn52Ser)

gnomAD frequency: 0.00238  dbSNP: rs143777403

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723959	SCV000230496	uncertain significance	not provided	2018-05-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000723959	SCV000516949	likely benign	not provided	2020-12-21	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22980763, 23041008, 26810512, 31931849, 32419263, 25891276, 26911675, 25326637, 23606453, 30564623, 30919934, 31517061)
Athena Diagnostics	RCV000723959	SCV000612355	uncertain significance	not provided	2023-03-29	criteria provided, single submitter	clinical testing	Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is higher than would generally be expected for pathogenic variants in this gene (http://gnomad.broadinstitute.org). In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086326	SCV000645894	benign	Gnathodiaphyseal dysplasia; Autosomal recessive limb-girdle muscular dystrophy type 2L	2024-01-26	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000723959	SCV000891959	uncertain significance	not provided	2024-07-01	criteria provided, single submitter	clinical testing	ANO5: PM3:Strong, PM2:Supporting, BP4
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000178421	SCV000923747	uncertain significance	not specified	2019-01-01	criteria provided, single submitter	clinical testing
Mendelics	RCV000988500	SCV001138247	uncertain significance	Gnathodiaphyseal dysplasia	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001108714	SCV001265983	uncertain significance	ANO5-Related Muscle Diseases	2017-08-24	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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Mayo Clinic Laboratories, Mayo Clinic	RCV000723959	SCV001714370	uncertain significance	not provided	2021-08-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000178421	SCV002512007	likely benign	not specified	2022-04-18	criteria provided, single submitter	clinical testing	Variant summary: ANO5 c.155A>G (p.Asn52Ser) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0022 in 251140 control in the gnomAD v2 database, including 2 homozygotes. Additionally, the variant allele was observed predominantly at a frequency of 0.0048 within the Latino subpopulation at in the gnomAD v3 database (genomes data). The observed variant frequency within Latino control individuals in the gnomAD v3 database is over one fold of the estimated maximal expected allele frequency for a pathogenic variant in ANO5 causing Limb-Girdle Muscular Dystrophy, Autosomal Recessive (0.0048 vs 0.0047), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. c.155A>G has been reported in the literature in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive (Sarkozy_2012, Sarkozy__2013, Wahbi_2013, Lee_2014, Savarese_2015, Nallamilli_2018, Ten Dam_2019, Mair_2020). These reports do not provide unequivocal conclusions about association of the variant with Limb-Girdle Muscular Dystrophy, Autosomal Recessive. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Ten ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=7), benign (n=1), likely benign (n=1) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as likely benign.
Dr.Nikuei Genetic Center	RCV000988500	SCV005200317	benign	Gnathodiaphyseal dysplasia	2024-06-29	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000723959	SCV001447710	likely pathogenic	not provided	2020-10-23	flagged submission	clinical testing