At the National Cancer Genetics MDT on 16th Sept 2021, and UK CGG council meeting 21st September 2021, clinical management of carriers of the variant BRCA1 c.5096G>A, (p.Arg1699Gln), (R1699Q) was discussed, given that epidemiological studies have shown that the associated risks have been found to be lower than those associated with other pathogenic/likely pathogenic variants in this gene.
The agreed national Consensus is that we should follow the proposed management guidelines in the JMG paper from ENIGMA*.
A summary of the recommendations from this paper is outlined here below:
For further information, click here to access the fulltext of the paper from the ENIGMA consortium*.
* Moghadasi S, Meeks HD, Vreeswijk MP, et al. The BRCA1 c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant: breast and ovarian cancer risk estimation and recommendations for clinical management from the ENIGMA consortium. J Med Genet. 2018 Jan;55(1):15-20. doi: 10.1136/jmedgenet-2017-104560. Epub 2017 May 10. PMID: 28490613.
Other variants associated with reduced penetrance have been reported in BRCA1, BRCA2 and other cancer predisposition genes. The absence of formal variant-specific epidemiological studies precludes generation of specific risk estimates and management guidelines.
Where a variant is known to be associated with reduced penetrance, this should be specified on the laboratory report. Recommendations for screening and/or risk reducing surgery in carriers of such variants should be individualised, and consider other factors such as personal and family history, and other lifestyle/environmental or co-existing genetic modifiers of disease.