ClinVar Miner

Submissions for variant NM_016011.4(MECR):c.830+2dup (rs756421370)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521566 SCV000616771 likely pathogenic not provided 2017-08-09 criteria provided, single submitter clinical testing The c.830+2dupT variant in the MECR gene has been reported in two unrelated families segregating an autosomal recessive form of childhood-onset dystonia with optic atrophy and basal ganglia abnormalities (Heimer et al., 2016). This variant destroys the canonical splice donor site in intron 7. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.830+2dupT variant is not observed at a significant frequency in large population cohorts and is not observed in the homozygous state in any individual within these cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.830+2dupT as a likely pathogenic variant.
Undiagnosed Diseases Network,NIH RCV000626033 SCV000746648 pathogenic Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities 2018-01-16 criteria provided, single submitter clinical testing Compound heterozygous variants, c.830+2dupT and c.-39G>C, were detected in this individual. The c.830+2dupT variant disrupts the splice donor consensus and has previously been reported as disease causing [PMID 27817865]. The c.-39G>C variant lies in the 5'UTR and has never been published to our knowledge. It is absent from large control databases. Whole exome and Sanger sequencing showed the mother is heterozygous for the c.830+2dupT variant and the father is heterozygous for the c.-39G>C variant. Whole exome and Sanger sequencing also showed the affected sibling is heterozygous for both variants in MECR. Our data indicate that the two variants in the MECR gene are in trans configuration (compound heterozygous) in this patient and the affected sibling.
OMIM RCV000626033 SCV000493966 pathogenic Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities 2017-01-07 no assertion criteria provided literature only
University of Washington Center for Mendelian Genomics,University of Washington RCV000755158 SCV000882980 likely pathogenic Optic atrophy; Childhood Onset Dystonias 2016-12-01 no assertion criteria provided research
GenomeConnect, ClinGen RCV000626033 SCV000986727 not provided Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities no assertion provided phenotyping only Variant interpretted as pathogenic and reported on 01/00/1900 by GTR ID Hudson Alpha Clinical Services Lab. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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