ArticleHuman genomics2025
Comprehensive bioinformatics analysis of selected germline variants of uncertain significance identified in a cohort of Sri Lankan hereditary breast cancer patients.
Article in Human genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Identification of Genetic Variants Among Breast Cancer Patients and At-Risk Individuals: A Cohort Study in Sri Lanka.Breast cancer : basic and clinical research · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNext-generation sequencing (NGS)-based testing is a cost-effective method for identifying pathogenic germline genetic variations in cancer-predisposing genes in hereditary breast cancer. However, many of the variants detected through NGS are classified as variants of uncertain significance (VUS), where the impact of the variants on protein function remains unclear. Bioinformatics analysis using multiple computational tools is postulated to aid in generating new knowledge regarding the functional relevance of these VUS. This study aimed to gain new insights into the potential pathogenicity of a selected set of VUS identified in a cohort of Sri Lankan hereditary breast cancer patients using advanced bioinformatics tools.
methodsThe cancer database at the Centre for Genetics and Genomics contains genomic and clinical data from patients who had undergone germline genetic testing between 2015 and 2023. Five germline VUS detected in breast cancer affected patients were identified from the existing database and selected for further bioinformatics analysis using a combination of in-silico pathogenicity prediction tools, 3D protein modeling with structural analysis, and protein structural stability assessment with molecular dynamic simulation (MDS). The VUS included: BRCA1:(NM_007294.4):c.3392A > G;p.Asp1131Gly, (rs1555587813); BRIP1:(NM_032043.3):c.3103C > T;p.Arg1035Cys, (rs45437094); CHEK2:(NM_007194.4):c.60G > T;p.Gln20His, (rs375507194); MET:(NM_000245.4):c.840G > T;p.Arg280Ser, (rs1207381066); and STK11:(NM_000455.5):c.355A > G;p.Asn119Asp, (rs545015076).
resultsTwo variants MET:(NM_000245.4):c.840G > T;p.Arg280Ser and BRCA1:(NM_007294.4):c.3392A > G; p.Asp1131Gly are predicted to have high-risk potential for causing significant impacts on the protein structure and function. Align GVGD results and the MDS data for the BRIP1:(NM_032043.3):c.3103C > T;p.Arg1035Cys variant suggested some alterations that require further confirmation. The CHEK2:(NM_007194.4):c.60G > T;p.Gln20His variant suggested an intermediate impact, whereas STK11:(NM_000455.5):c.355A > G;p.Asn119Asp suggested no significant structural or functional impact on the protein.
conclusionsThis study contributes valuable insights into the potential structural and functional implications of five VUS in cancer predisposition genes. Our results suggest a high-risk potential for variants in MET, BRCA1 and BRIP1, warranting further investigation to delineate their exact biological effects and to better understand their role in breast cancer risk.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.