ClinVar Miner

Submissions for variant NM_213599.2(ANO5):c.2004del (p.Leu669fs) (rs886043172)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000523626 SCV000338804 pathogenic not provided 2017-04-19 criteria provided, single submitter clinical testing
GeneDx RCV000523626 SCV000617770 pathogenic not provided 2018-09-18 criteria provided, single submitter clinical testing The c.2004delG variant in the ANO5 gene has been reported previously in 2 unrelated individuals with ANO5-muscular dystrophy who also harbored a second ANO5 variant; however phase was undetermined (Liewluck et al., 2013). The c.2004delG variant is not observed in large population cohorts (Lek et al., 2016). The c.2004delG variant causes a frameshift starting with codon Leucine 669, changes this amino acid to a Phenylalanine residue and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Leu669PhefsX6. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, we interpret c.2004delG as a pathogenic variant.
Invitae RCV000700782 SCV000829553 pathogenic Gnathodiaphyseal dysplasia; Limb-girdle muscular dystrophy, type 2L 2018-05-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu669Phefs*6) in the ANO5 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in combination with other ANO5 variants in individuals affected with ANO5-related muscular dystrophy (PMID:23663589). ClinVar contains an entry for this variant (Variation ID: 285669). Loss-of-function variants in ANO5 are known to be pathogenic (PMID: 21186264, 23606453, 25891276). For these reasons, this variant has been classified as Pathogenic.

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