ClinVar Miner

Submissions for variant NM_001003800.2(BICD2):c.1489_1491delinsTCA (p.Glu497Ser)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002389644 SCV002698607 uncertain significance Inborn genetic diseases 2019-10-02 criteria provided, single submitter clinical testing The c.1489_1491delGAGinsTCA variant (also known as p.E497S), located in coding exon 5 of the BICD2 gene, results from an in-frame deletion of GAG and insertion of TCA at nucleotide positions 1489 to 1491. This results in the substitution of the glutamic acid residue for a serine residue at codon 497, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Illumina Laboratory Services, Illumina RCV003408265 SCV004123271 uncertain significance Spinal muscular atrophy, lower extremity-predominant, 2b, prenatal onset, autosomal dominant 2023-06-14 criteria provided, single submitter clinical testing The BICD2 c.1489_1491delinsTCA, p.(Glu497Ser) missense variant has not, to our knowledge, been reported in the peer-reviewed literature. This variant lies in the middle region of the BICD2 protein that has been shown to interact with the KIF5A protein which is a microtubule motor involved in intracellular organelle transport (PMID: 20386726). Additionally, nearby missense variants such as p.Arg501Pro (ClinVar variation ID: 55862) and p.Lys508Thr (ClinVar variation ID: 55861) have been reported in the literature in multiple individuals with phenotypes consistent with spinal muscular atrophy and spastic paraplegia (PMID: 23664120; 25497877; 31127727). This variant is not observed in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. Based on the available evidence, the c.1489_1491delinsTCA, p.(Glu497Ser) variant is classified as a variant of uncertain significance for spinal muscular atrophy, lower extremity predominant.

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