Journal article
Multifactorial likelihood assessment of BRCA1 and BRCA2 missense variants confirms that BRCA1:c.122A>G(p.His41Arg) is a pathogenic mutation
PJ Whiley, MT Parsons, J Leary, K Tucker, L Warwick, B Dopita, H Thorne, SR Lakhani, DE Goldgar, MA Brown, AB Spurdle
Plos One | Published : 2014
Abstract
Rare exonic, non-truncating variants in known cancer susceptibility genes such as BRCA1 and BRCA2 are problematic for genetic counseling and clinical management of relevant families. This study used multifactorial likelihood analysis and/or bioinformatically-directed mRNA assays to assess pathogenicity of 19 BRCA1 or BRCA2 variants identified following patient referral to clinical genetic services. Two variants were considered to be pathogenic (Class 5). BRCA1:c.4484G> C(p.Arg1495Thr) was shown to result in aberrant mRNA transcripts predicted to encode truncated proteins. The BRCA1:c.122A>G(p. His41Arg) RING-domain variant was found from multifactorial likelihood analysis to have a posterior..
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Awarded by National Institutes of Health
Funding Acknowledgements
The Clinical Follow Up Study was funded 2001-2009 by NHMRC (www.nhmrc.gov.au) and currently by the National Breast Cancer Foundation (www.nbcf.org.au) and Cancer Australia (www.canceraustralia.gov.au) # 628333. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. This work was supported in part by project grants from The National Health and Medical Research Council (NHMRC, ID442970 & ID1010719) to Amanda B. Spurdle who is supported by an NHMRC Senior Research Fellowship. David E. Goldgar was supported by National Institutes of Health (NIH) (www.nih.gov) grant CA116167, an NIH Recovery Act supplement (CA116167Z) and an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.