| Title: |
Clinical variants paired with phenotype: Arichresource for brain gene curation |
| Authors: |
Chopra, Maya; Savatt, Juliann M; Bingaman, Taylor I; Good, Molly E; Morgan, Alexis; Cooney, Caitlin; Rossel, Allison M; VanHoute, Bryanna; Cordova, Ineke; Mahida, Sonal; Lanzotti, Virginia; Baldridge, Dustin; Gurnett, Christina A; Piven, Joseph; Hazlett, Heather; Pomeroy, Scott L; Sahin, Mustafa; Payne, Philip RO; Riggs, Erin Rooney; Constantino, John N; Consortium, Brain Gene Registry; Gropman, A; Smith-Hicks, CL; Neul, J; Agosto, JA Martinez-; German, K; Izumi, K; Abbeduto, L; Dawalt, L; Wangler, M; Wasserstein, M; Storch, Eric A; Cohen, JS; Samaco, R; Molholm, S; Shankar, S; Srivastava, S; Walkley, S; Sveden, A; Dies, K; Gupta, Aditi; Oh, Inez; Hauck, Rachel |
| Source: |
Genetics in Medicine, vol 26, iss 3 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2024 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
31 Biological Sciences (for-2020); 3105 Genetics (for-2020); Neurosciences (rcdc); Genetics (rcdc); Clinical Research (rcdc); 3 Good Health and Well Being (sdg); Humans (mesh); Genetic Variation (mesh); Databases; Genetic (mesh); Genetic Testing (mesh); Phenotype (mesh); Brain (mesh); Brain Gene Registry Consortium; Autism; Gene curation; Intellectual disability; Neurodevelopmental disorders; Variant of uncertain significance; 0604 Genetics (for); 1103 Clinical Sciences (for); Genetics & Heredity (science-metrix) |
| Description: |
PURPOSE: Clinically ascertained variants are under-utilized in neurodevelopmental disorder research. We established the Brain Gene Registry (BGR) to coregister clinically identified variants in putative brain genes with participant phenotypes. Here, we report 179 genetic variants in the first 179 BGR registrants and analyze the proportion that were novel to ClinVar at the time of entry and those that were absent in other disease databases. METHODS: From 10 academically affiliated institutions, 179 individuals with 179 variants were enrolled into the BGR. Variants were cross-referenced for previous presence in ClinVar and for presence in 6 other genetic databases. RESULTS: Of 179 variants in 76 genes, 76 (42.5%) were novel to ClinVar, and 62 (34.6%) were absent from all databases analyzed. Of the 103 variants present in ClinVar, 37 (35.9%) were uncertain (ClinVar aggregate classification of variant of uncertain significance or conflicting classifications). For 5 variants, the aggregate ClinVar classification was inconsistent with the interpretation from the BGR site-provided classification. CONCLUSION: A significant proportion of clinical variants that are novel or uncertain are not shared, limiting the evidence base for new gene-disease relationships. Registration of paired clinical genetic test results with phenotype has the potential to advance knowledge of the relationships between genes and neurodevelopmental disorders. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt8k68d1b9; https://escholarship.org/uc/item/8k68d1b9; https://escholarship.org/content/qt8k68d1b9/qt8k68d1b9.pdf |
| DOI: |
10.1016/j.gim.2023.101035 |
| Availability: |
https://escholarship.org/uc/item/8k68d1b9; https://escholarship.org/content/qt8k68d1b9/qt8k68d1b9.pdf; https://doi.org/10.1016/j.gim.2023.101035 |
| Rights: |
CC-BY-NC-ND |
| Accession Number: |
edsbas.273E4F1D |
| Database: |
BASE |