ClinVar Miner

Submissions for variant NM_014043.4(CHMP2B):c.56G>A (p.Arg19Gln)

gnomAD frequency: 0.00006  dbSNP: rs200322526
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001148367 SCV001309257 likely benign Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV001148367 SCV002272944 uncertain significance Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 2024-10-15 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 19 of the CHMP2B protein (p.Arg19Gln). This variant is present in population databases (rs200322526, gnomAD 0.02%). This missense change has been observed in individual(s) with parkinsonism-dementia complex (PMID: 25558820). ClinVar contains an entry for this variant (Variation ID: 902088). 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 tolerated. 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.
Revvity Omics, Revvity RCV001148367 SCV003832012 uncertain significance Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 2019-09-24 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003953530 SCV004783076 uncertain significance CHMP2B-related disorder 2024-02-05 no assertion criteria provided clinical testing The CHMP2B c.56G>A variant is predicted to result in the amino acid substitution p.Arg19Gln. This variant was reported in an individual with parkinsonism-dementia complex but was also observed in two unaffected controls age 57 and 71 (Steele et al 2015. PubMed ID: 25558820). This variant is reported in 0.020% of alleles in individuals of East Asian descent in gnomAD. This variant could be benign. 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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