ClinVar Miner

Submissions for variant NM_001122955.4(BSCL2):c.1004A>C (p.Gln335Pro)

gnomAD frequency: 0.00001  dbSNP: rs779199750
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001224191 SCV001396375 likely pathogenic Charcot-Marie-Tooth disease type 2 2025-01-10 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 271 of the BSCL2 protein (p.Gln271Pro). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or altered protein product. This variant is present in population databases (rs779199750, gnomAD 0.002%). This missense change has been observed in individual(s) with clinical features of autosomal recessive BSCL2-related conditions (PMID: 30150100). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.1004A>C (p.Gln335Pro). ClinVar contains an entry for this variant (Variation ID: 952140). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Studies have shown that this missense change results in skipping of exon 7, and produces a non-functional protein and/or introduces a premature termination codon (PMID: 30150100). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV002418777 SCV002678267 uncertain significance Inborn genetic diseases 2021-01-13 criteria provided, single submitter clinical testing The p.Q271P variant (also known as c.812A>C), located in coding exon 6 of the BSCL2 gene, results from an A to C substitution at nucleotide position 812. The glutamine at codon 271 is replaced by proline, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005050293 SCV005684448 likely pathogenic Congenital generalized lipodystrophy type 2; Hereditary spastic paraplegia 17; Severe neurodegenerative syndrome with lipodystrophy; Neuronopathy, distal hereditary motor, type 5C 2024-01-30 criteria provided, single submitter clinical testing

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