Exceptions to the rule: Case studies in the prediction of pathogenicity for genetic variants in hereditary cancer genes

Clinical Genetics

Volumn 88, Issue 6, 2015, Pages 533-541

  Rosenthal, E T ^a   Bowles, K R ^a   Pruss, D ^a   van Kan, A ^a   Vail, P J ^a   McElroy, H ^a   Wenstrup, R J ^a  

^a Utah   (United States)

Author keywords

BRCA1; BRCA2; Genetic variant; Hereditary neoplastic syndromes; MSH2; Variant classification

Indexed keywords

BRCA1 PROTEIN; BRCA2 PROTEIN; PROTEIN MSH2; MSH2 PROTEIN, HUMAN;

ARTICLE; CLASSIFICATION ALGORITHM; EXON; EXON SKIPPING; FAMILIAL CANCER; GENETIC ALGORITHM; GENETIC VARIABILITY; HUMAN; INTRON; PATHOGENICITY; PENETRANCE; PRACTICE GUIDELINE; PREDICTIVE VALUE; PRIORITY JOURNAL; RNA SPLICING; START CODON; TUMOR GENE; GENETIC PREDISPOSITION; GENETIC SCREENING; GENETIC VARIATION; GENETICS; NEOPLASMS; PROCEDURES; PROGNOSIS; REPRODUCIBILITY; SENSITIVITY AND SPECIFICITY; STANDARDS; STATISTICS AND NUMERICAL DATA;

BRCA1 PROTEIN; BRCA2 PROTEIN; GENETIC PREDISPOSITION TO DISEASE; GENETIC TESTING; GENETIC VARIATION; HUMANS; MUTS HOMOLOG 2 PROTEIN; NEOPLASMS; PRACTICE GUIDELINES AS TOPIC; PREDICTIVE VALUE OF TESTS; PROGNOSIS; REPRODUCIBILITY OF RESULTS; SENSITIVITY AND SPECIFICITY;

EID: 84946498881     PISSN: 00099163     EISSN: 13990004     Source Type: Journal    
DOI: 10.1111/cge.12560     Document Type: Article

References (26)

1. Richards CS, Bale S, Bellissimo DB et al. ACMG recommendations for standards for interpretation and reporting of sequence variations: revisions 2007. Genet Med 2008: 10: 294-300.
2. Eggington JM, Bowles KR, Moyes K et al. A comprehensive laboratory-based program for classification of variants of uncertain significance in hereditary cancer genes. Clin Genet 2014: 86: 229-237.
3. Goldgar DE, Easton DF, Byrnes GB, Spurdle AB, Iversen ES, Greenblatt MS. Genetic evidence and integration of various data sources for classifying uncertain variants into a single model. Hum Mutat 2008: 29: 1265-1272.
4. Easton DF, Deffenbaugh AM, Pruss D et al. A systematic genetic assessment of 1, 433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes. Am J Hum Genet 2007: 81: 873-883.
5. Pruss D, Morris B, Hughes E et al. Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes. Breast Cancer Res Treat 2014: 147: 119-132.
6. Tavtigian SV, Samollow PB, de Silva D, Thomas A. An analysis of unclassified missense substitutions in human BRCA1. Fam Cancer 2006: 5: 77-88.
7. Thompson D, Easton DF, Goldgar DE. A full-likelihood method for the evaluation of causality of sequence variants from family data. Am J Hum Genet 2003: 73: 652-655.
8. Shapiro MB, Senapathy P. RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. Nucleic Acids Res 1987: 15: 7155-7174.
9. Tesoriero AA, Wong EM, Jenkins MA et al. Molecular characterization and cancer risk associated with BRCA1 and BRCA2 splice site variants identified in multiple-case breast cancer families. Hum Mutat 2005: 26: 495.
10. Dosil V, Tosar A, Canadas C et al. Alternative splicing and molecular characterization of splice site variants: BRCA1 c.591C>T as a case study. Clin Chem 2010: 56: 53-61.
11. Colombo M, Blok MJ, Whiley P et al. Comprehensive annotation of splice junctions supports pervasive alternative splicing at the BRCA1 locus: a report from the ENIGMA consortium. Hum Mol Genet 2014: 23: 3666-3680.
12. Sawyer SL, Tian L, Kahkonen M et al. Biallelic mutations in BRCA1 cause a new Fanconi anemia subtype. Cancer Discov 2014: doi:10.1158/2159-8290.CD-14-1156.
13. Biswas K, Das R, Eggington JM et al. Functional evaluation of BRCA2 variants mapping to the PALB2-binding and C-terminal DNA-binding domains using a mouse ES cell-based assay. Hum Mol Genet 2012: 21: 3993-4006.
14. Howlett NG, Taniguchi T, Olson S et al. Biallelic inactivation of BRCA2 in Fanconi anemia. Science 2002: 297: 606-609.
15. Dasouki M, Penning K, Shwaiki A, Mundt S. Fanconi anemia D1 presenting as breast cancer caused by bi-allelic BRCA2 gene mutations. San Diego, CA: American Society of Human Genetics Annual Meeting, 2007.
16. Myriad Genetic Laboratories. Internal Data. 2013.
17. Farrington SM, Lin-Goerke J, Ling J et al. Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients and controls. Am J Hum Genet 1998: 63: 749-759.
18. Barnetson RA, Cartwright N, van Vliet A et al. Classification of ambiguous mutations in DNA mismatch repair genes identified in a population-based study of colorectal cancer. Hum Mutat 2008: 29: 367-374.
19. Kets CM, Hoogerbrugge N, van Krieken JH, Goossens M, Brunner HG, Lightenbert MJ. Compound heterozygosity for two MSH2 mutations suggests mild consequences of the initiation codon variant c.1A>G of MSH2. Eur J Hum Genet 2009: 17: 159-164.
20. Cyr JL, Brown GD, Stroop J, Heinen CD. The predicted truncation from a cancer-associated variant of the MSH2 initiation codon alters activity of the MSH2-MSH6 mismatch repair complex. Mol Carcinog 2012: 51: 647-658.
21. Plon SE, Eccles DM, Easton D et al. Sequence variant classification and reporting: recommendations for improving the interpretation of cancer susceptibility genetic test results. Hum Mutat 2008: 29: 1282-1291.
22. Shirts BH, Jacobson A, Jarvik GP, Browning BL. Large numbers of individuals are required to classify and define risk for rare variants in known cancer risk genes. Genet Med 2014: 16: 529-534.
23. Spurdle AB, Whiley PJ, Thompson B et al. BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk. J Med Genet 2012: 49: 525-532.
24. Lindor NM, Guidugli L, Wang X et al. A review of a multifactorial probability-based model for classification of BRCA1 and BRCA2 variants of uncertain significance (VUS). Hum Mutat 2012: 33: 8-21.
25. Bell J, Bodmer D, Sistermans E, Ramsden SC. Practice guidelines for the Interpretation and Reporting of Unclassified Variants (UVs) in Clinical Molecular Genetics. Best Practice Guidelines: Clinical Molecular Genetics Society, 2007.
26. College of American Pathologists. Molecular Pathology Checklist: CAP Accreditation Program. College of American Pathologists, 2013.