ClinVar Miner

Submissions for variant NM_002488.4(NDUFA2):c.225del (p.Asn76fs) (rs863224084)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514072 SCV000610210 uncertain significance not provided 2017-05-30 criteria provided, single submitter clinical testing
GeneDx RCV000514072 SCV000251792 uncertain significance not provided 2017-03-15 criteria provided, single submitter clinical testing The c.225delG variant in the NDUFA2 gene has been reported previously with a NDUFA2 missense variant (phase unknown) in a one year old child with failure to thrive, developmental regression, and progressive white matter demyelination (Vanderver et al., 2016). As the demyelination involved selective brainstem tracts suggestive of a mitochondral encephalopathy, the authors concluded the NDUFA2 variants were likely pathogenic (Vanderver et al., 2016). The c.225delG causes a frameshift starting with codon Asparagine 76, changes this amino acid to a Methionine residue, and creates a premature Stop codon at position 4 of the new reading frame, denoted p.Asn76MetfsX4. This variant is predicted to cause loss of normal protein function through protein truncation. The c.225delG variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.225delG as a variant of uncertain significance.
MyeliNeuroGene Lab,McGill University Health Center Research Institute RCV000515932 SCV000584199 pathogenic Cystic Leukoencephalopathy criteria provided, single submitter research This is the first report of autosomal recessive mutations in NDUFA2 associated with cystic leukoencephalopathy.

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