ClinVar Miner

Submissions for variant NM_014043.4(CHMP2B):c.218C>T (p.Thr73Met)

gnomAD frequency: 0.00014  dbSNP: rs192188850
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000390491 SCV000446337 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.
Athena Diagnostics Inc RCV000516998 SCV000612726 uncertain significance not specified 2017-05-19 criteria provided, single submitter clinical testing
Invitae RCV000390491 SCV000952963 uncertain significance Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 73 of the CHMP2B protein (p.Thr73Met). This variant is present in population databases (rs192188850, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CHMP2B-related conditions. ClinVar contains an entry for this variant (Variation ID: 346806). 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. 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.
PreventionGenetics, part of Exact Sciences RCV003401367 SCV004119914 uncertain significance CHMP2B-related condition 2023-06-20 criteria provided, single submitter clinical testing The CHMP2B c.218C>T variant is predicted to result in the amino acid substitution p.Thr73Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.014% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-87294955-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.