ClinVar Miner

Submissions for variant NM_018075.5(ANO10):c.132dup (p.Asp45fs) (rs540331226)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000311100 SCV000329065 pathogenic not provided 2020-05-18 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate that the variant results in a significant reduction of ANO10 expression (Balreira et al., 2014).; This variant is associated with the following publications: (PMID: 25664551, 27045840, 25133958, 25182700, 25089919, 25664549, 29482223, 29915382, 30515630, 31423897, 31980526)
Genetic Services Laboratory, University of Chicago RCV000149437 SCV000593208 pathogenic Spinocerebellar ataxia, autosomal recessive 10 2016-11-02 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000311100 SCV000612337 pathogenic not provided 2020-05-11 criteria provided, single submitter clinical testing The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and found in general population data at a frequency that is consistent with pathogenicity. 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000311100 SCV000862732 pathogenic not provided 2018-08-01 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000825557 SCV000966877 pathogenic Autosomal recessive cerebellar ataxia 2018-05-10 criteria provided, single submitter clinical testing The p.Asp45fs variant in ANO10 has been previously reported in 6 compound hetero zygous individuals and 2 homozygous individuals with adult-onset autosomal reces sive spinocerebellar ataxia (Renaud 2014, Balreira 2014, Fogel 2014, Minnerop 20 15). This variant has also been identified in 0.08% (12/14786) of European chrom osomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute. org; dbSNP rs540331226). Although this variant has been seen in the general popu lation, its frequency is low enough to be consistent with a recessive carrier fr equency for autosomal recessive spinocerebellar ataxia. This variant has also be en reported by other clinical laboratories in ClinVar (Variation ID: 162016). Th is variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 45 and leads to a premature termination codo n 9 amino acids downstream. This alteration is then predicted to lead to a trunc ated or absent protein. In summary, the p.Asp45fs variant meets criteria to be c lassified as pathogenic for adult-onset autosomal recessive spinocerebellar atax ia. ACMG/AMP Criteria applied: PVS1; PM3_Strong.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000311100 SCV001249875 pathogenic not provided 2019-03-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000311100 SCV001447379 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital RCV000311100 SCV001449599 likely pathogenic not provided 2015-05-26 criteria provided, single submitter clinical testing
Greenwood Genetic Center Diagnostic Laboratories,Greenwood Genetic Center RCV000311100 SCV001468025 pathogenic not provided 2020-08-12 criteria provided, single submitter clinical testing
Invitae RCV000311100 SCV001579504 pathogenic not provided 2020-03-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asp45Argfs*9) in the ANO10 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individual(s) with clinical features of cerebellar ataxia (PMID: 25089919, 25133958, 25182700). This variant is also known as c.123_124insA and c.132_133insT in the literature. ClinVar contains an entry for this variant (Variation ID: 162016). Loss-of-function variants in ANO10 are known to be pathogenic (PMID: 25089919). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000149437 SCV000196075 pathogenic Spinocerebellar ataxia, autosomal recessive 10 2014-11-01 no assertion criteria provided literature only
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000149437 SCV000965816 likely pathogenic Spinocerebellar ataxia, autosomal recessive 10 no assertion criteria provided clinical testing

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