ClinVar Miner

Submissions for variant NM_213599.3(ANO5):c.1630+2T>G

dbSNP: rs1590300702
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001004964 SCV001164502 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2L 2018-12-03 criteria provided, single submitter research The homozygous c.1630+2T>G variant in ANO5 was identified by our study in one individual with limb-girdle muscular dystrophy (LGMD). This variant was absent from large population studies. The c.1630+2T>G variant occurs in the invariant region (+/- 1/2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. However, this information is not predictive enough to determine pathogenicity. Loss of function of the ANO5 gene is an established disease mechanism in autosomal recessive LGMD. In summary, although additional studies are required to fully establish its clinical significance, the c.1630+2T>G variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PVS1 (Richards 2015).
Invitae RCV001862746 SCV002277530 likely pathogenic Gnathodiaphyseal dysplasia; Autosomal recessive limb-girdle muscular dystrophy type 2L 2023-05-15 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 813973). This variant has not been reported in the literature in individuals affected with ANO5-related conditions. This sequence change affects a donor splice site in intron 15 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).

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