ClinVar Miner

Submissions for variant NM_001122955.4(BSCL2):c.844G>A (p.Ala282Thr)

gnomAD frequency: 0.00014  dbSNP: rs190842600
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000554606 SCV000657780 uncertain significance Charcot-Marie-Tooth disease type 2 2024-01-20 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 218 of the BSCL2 protein (p.Ala218Thr). This variant is present in population databases (rs190842600, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with BSCL2-related conditions. ClinVar contains an entry for this variant (Variation ID: 476815). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BSCL2 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen RCV000994647 SCV001148306 uncertain significance not provided 2023-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000994647 SCV001825387 uncertain significance not provided 2020-12-03 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genetic Services Laboratory, University of Chicago RCV001821649 SCV002067031 uncertain significance not specified 2017-10-18 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001848974 SCV002106260 uncertain significance Hereditary spastic paraplegia 2017-10-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV002367959 SCV002660565 uncertain significance Inborn genetic diseases 2022-03-29 criteria provided, single submitter clinical testing The p.A218T variant (also known as c.652G>A), located in coding exon 5 of the BSCL2 gene, results from a G to A substitution at nucleotide position 652. The alanine at codon 218 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the supporting evidence, this variant is unlikely to be causative of autosomal dominant BSCL2-related neurologic disorders; however, its contribution to the development of autosomal recessive BSCL2-related syndrome is uncertain.
Baylor Genetics RCV003147507 SCV003836118 uncertain significance Congenital generalized lipodystrophy type 2 2022-01-06 criteria provided, single submitter clinical testing
Breakthrough Genomics, Breakthrough Genomics RCV000994647 SCV005191320 uncertain significance not provided criteria provided, single submitter not provided

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