ClinVar Miner

Submissions for variant NM_001003800.2(BICD2):c.1636_1638del (p.Asn546del) (rs1064795760)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481650 SCV000571877 likely pathogenic not provided 2016-10-17 criteria provided, single submitter clinical testing The c.1636_1638delAAT variant results in an in-frame 3 base pair deletion and is predicted to cause loss of an evolutionarily conserved Asparagine residue at position 546 in the protein, denoted as p.Asn546del. The c.1636_1638delAAT variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.1636_1638delAAT variant is a strong candidate for a pathogenic variant.
Institute for Genomic Medicine, Nationwide Children's Hospital RCV000627061 SCV000715101 likely pathogenic Seizures; Feeding difficulties; Muscle weakness; EEG abnormality; Tapered finger; Absent speech; Open mouth; Macrocephalus; Decreased fetal movement; Cerebral cortical atrophy; Downturned corners of mouth; Recurrent fractures; Arthrogryposis multiplex congenita; Skeletal muscle atrophy 2018-04-04 criteria provided, single submitter research The c.1636_1638delAAT variant results in an in-frame 3 base pair deletion and is predicted to cause loss of an evolutionarily conserved Asparagine residue in a non-repetitive region of the protein (p.Asn546del). It has not been reported in large population cohorts such as gnomAD. In silico modeling suggests that removing the Asn546 disrupts protein secondary structure in a region that has been shown (in mice) to bind KIF5A. This mutation occurred de novo in our patient and was reported by GeneDx in an unrelated patient who shared similar features. We therefore interpret the variant as likely pathogenic.
Ambry Genetics RCV001267512 SCV001445693 pathogenic Inborn genetic diseases 2019-07-19 criteria provided, single submitter clinical testing
OMIM RCV000754663 SCV000882586 pathogenic Spinal muscular atrophy, lower extremity-predominant, 2b, prenatal onset, autosomal dominant 2019-01-30 no assertion criteria provided literature only

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