ClinVar Miner

Submissions for variant NM_014043.4(CHMP2B):c.206G>A (p.Arg69Gln)

gnomAD frequency: 0.00011  dbSNP: rs200792883
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001092352 SCV001248813 pathogenic not provided 2016-09-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001241565 SCV001414592 uncertain significance Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 2023-06-09 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with progressive muscular atrophy, amyotrophic lateral sclerosis, and vascular dementia (PMID: 20625756, 23155438, 28430856, 29525180). This variant is present in population databases (rs200792883, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 69 of the CHMP2B protein (p.Arg69Gln). ClinVar contains an entry for this variant (Variation ID: 872081). 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. 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.
GeneDx RCV001092352 SCV001986326 uncertain significance not provided 2019-09-19 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26843957, 28430856, 20625756, 29525180, 23155438)
PreventionGenetics, part of Exact Sciences RCV004746237 SCV005353024 uncertain significance CHMP2B-related disorder 2024-09-19 no assertion criteria provided clinical testing The CHMP2B c.206G>A variant is predicted to result in the amino acid substitution p.Arg69Gln. This variant has been reported in three individuals presenting with either vascular dementia, ALS, or progressive muscular atrophy (van Blitterswijk et al. 2012. PubMed ID: 23155438; Morgan et al. 2017. PubMed ID: 28430856; Bartoletti-Stella et al. 2018. PubMed ID: 29525180). This variant is reported in 0.013% of alleles in individuals of South Asian descent in gnomAD and in one control patient (Ghanim et al. 2010. PubMed ID: 20625756). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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