ClinVar Miner

Submissions for variant NM_006796.3(AFG3L2):c.1749G>A (p.Trp583Ter)

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Total submissions: 3
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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 RCV002509896 SCV003761383 likely pathogenic Spastic ataxia 5 2023-01-25 criteria provided, single submitter curation The heterozygous p.Trp583Ter variant in AFG3L2 was identified by our study, in the compound heterozygous state with a likely pathogenic variant (ClinVar Variation ID: 162524), in one individual with spastic ataxia. Familial genome analysis revealed that this variant was in trans with a likely pathogenic variant (ClinVar Variation ID: 162524). The p.Trp583Ter variant in AFG3L2 has not been previously reported in individuals with spastic ataxia 5. This variant was absent from large population studies. This nonsense variant leads to a premature termination codon at position 583, which is predicted to lead to a truncated or absent protein. Loss of function of the AFG3L2 gene is strongly associated to autosomal recessive spastic ataxia 5. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for spastic ataxia 5. ACMG/AMP Criteria applied: PVS1_Strong, PM2_Supporting, PM3 (Richards 2015).
Revvity Omics, Revvity RCV003146577 SCV003831232 likely pathogenic not provided 2023-07-21 criteria provided, single submitter clinical testing
Undiagnosed Diseases Network, NIH RCV002509896 SCV002818547 likely pathogenic Spastic ataxia 5 2022-08-03 no assertion criteria provided clinical testing

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