Submissions for variant NM_213599.3(ANO5):c.40+2T>C

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Revvity Omics, Revvity	RCV003132915	SCV003809610	likely pathogenic	not provided	2022-01-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003778733	SCV004604869	likely pathogenic	Gnathodiaphyseal dysplasia; Autosomal recessive limb-girdle muscular dystrophy type 2L	2023-02-10	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 1 of the ANO5 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ANO5 are known to be pathogenic (PMID: 21186264, 23606453, 25891276, 30919934). This variant is present in population databases (rs760033003, gnomAD 0.0008%). This variant has not been reported in the literature in individuals affected with ANO5-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.