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BRCA Variant of Unknown Significance

MedGen UID:
1710820
•Concept ID:
C5238257
•
Cell or Molecular Dysfunction
Synonyms: BRCA Family Gene VUS; BRCA Family VUS; BRCA Gene Family VUS; BRCA Gene Variant of Unknown Significance; BRCA Gene VUS; BRCA VUS; VUS BRCA

Definition

A change in the nucleotide sequence of a gene in the BRCA family whose association with disease risk is unknown or uncertain. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVBRCA Variant of Unknown Significance

Professional guidelines

PubMed

Treatment of women with BRCA mutation.
Depypere H
Climacteric 2023 Jun;26(3):235-239. Epub 2023 Apr 3 doi: 10.1080/13697137.2023.2189583. PMID: 37011662
Mutations of BRCA1/2 Genes in the West of Turkey and Genotype-Phenotype Correlations.
Gun-Bilgic D, Aydin-Gumus A, Bilgic A, Cam FS
Clin Lab 2022 Jan 1;68(1) doi: 10.7754/Clin.Lab.2021.210425. PMID: 35023674
Implementation of a risk assessment program in a breast-imaging community practice.
Destounis S, Arieno A, Morgan R
Breast Cancer 2016 Mar;23(2):273-8. Epub 2014 Oct 7 doi: 10.1007/s12282-014-0569-4. PMID: 25287518

Recent clinical studies

Etiology

Treatment of women with BRCA mutation.
Depypere H
Climacteric 2023 Jun;26(3):235-239. Epub 2023 Apr 3 doi: 10.1080/13697137.2023.2189583. PMID: 37011662
BRCA1/2 variants of unknown significance in hereditary breast and ovarian cancer (HBOC) syndrome: Looking for the hidden meaning.
Fanale D, Pivetti A, Cancelliere D, Spera A, Bono M, Fiorino A, Pedone E, Barraco N, Brando C, Perez A, Guarneri MF, Russo TDB, Vieni S, Guarneri G, Russo A, Bazan V
Crit Rev Oncol Hematol 2022 Apr;172:103626. Epub 2022 Feb 10 doi: 10.1016/j.critrevonc.2022.103626. PMID: 35150867
Germline Mutation in 1338 BRCA-Negative Chinese Hereditary Breast and/or Ovarian Cancer Patients: Clinical Testing with a Multigene Test Panel.
Kwong A, Shin VY, Chen J, Cheuk IWY, Ho CYS, Au CH, Chan KKL, Ngan HYS, Chan TL, Ford JM, Ma ESK
J Mol Diagn 2020 Apr;22(4):544-554. Epub 2020 Feb 15 doi: 10.1016/j.jmoldx.2020.01.013. PMID: 32068069
BRCA mutations: is everything said?
López-Urrutia E, Salazar-Rojas V, Brito-Elías L, Coca-González M, Silva-García J, Sánchez-Marín D, Campos-Parra AD, Pérez-Plasencia C
Breast Cancer Res Treat 2019 Jan;173(1):49-54. Epub 2018 Oct 6 doi: 10.1007/s10549-018-4986-5. PMID: 30293211
A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes.
Easton DF, Deffenbaugh AM, Pruss D, Frye C, Wenstrup RJ, Allen-Brady K, Tavtigian SV, Monteiro AN, Iversen ES, Couch FJ, Goldgar DE
Am J Hum Genet 2007 Nov;81(5):873-83. Epub 2007 Sep 6 doi: 10.1086/521032. PMID: 17924331Free PMC Article

Diagnosis

Treatment of women with BRCA mutation.
Depypere H
Climacteric 2023 Jun;26(3):235-239. Epub 2023 Apr 3 doi: 10.1080/13697137.2023.2189583. PMID: 37011662
BRCA1/2 variants of unknown significance in hereditary breast and ovarian cancer (HBOC) syndrome: Looking for the hidden meaning.
Fanale D, Pivetti A, Cancelliere D, Spera A, Bono M, Fiorino A, Pedone E, Barraco N, Brando C, Perez A, Guarneri MF, Russo TDB, Vieni S, Guarneri G, Russo A, Bazan V
Crit Rev Oncol Hematol 2022 Apr;172:103626. Epub 2022 Feb 10 doi: 10.1016/j.critrevonc.2022.103626. PMID: 35150867
Germline Mutation in 1338 BRCA-Negative Chinese Hereditary Breast and/or Ovarian Cancer Patients: Clinical Testing with a Multigene Test Panel.
Kwong A, Shin VY, Chen J, Cheuk IWY, Ho CYS, Au CH, Chan KKL, Ngan HYS, Chan TL, Ford JM, Ma ESK
J Mol Diagn 2020 Apr;22(4):544-554. Epub 2020 Feb 15 doi: 10.1016/j.jmoldx.2020.01.013. PMID: 32068069
New challenges for BRCA testing: a view from the diagnostic laboratory.
Wallace AJ
Eur J Hum Genet 2016 Sep;24 Suppl 1(Suppl 1):S10-8. doi: 10.1038/ejhg.2016.94. PMID: 27514839Free PMC Article
Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants.
Houdayer C, Caux-Moncoutier V, Krieger S, Barrois M, Bonnet F, Bourdon V, Bronner M, Buisson M, Coulet F, Gaildrat P, Lefol C, Léone M, Mazoyer S, Muller D, Remenieras A, Révillion F, Rouleau E, Sokolowska J, Vert JP, Lidereau R, Soubrier F, Sobol H, Sevenet N, Bressac-de Paillerets B, Hardouin A, Tosi M, Sinilnikova OM, Stoppa-Lyonnet D
Hum Mutat 2012 Aug;33(8):1228-38. Epub 2012 May 11 doi: 10.1002/humu.22101. PMID: 22505045

Therapy

Clinical outcomes and response to chemotherapy in a cohort of pancreatic cancer patients with germline variants of unknown significance (VUS) in BRCA1 and BRCA2 genes.
Militello AM, Orsi G, Cavaliere A, Niger M, Avallone A, Salvatore L, Tortora G, Rapposelli IG, Giordano G, Noventa S, Giommoni E, Bozzarelli S, Macchini M, Peretti U, Procaccio L, Puccini A, Cascinu S, Montagna C, Milella M, Reni M
Cancer Chemother Pharmacol 2023 Dec;92(6):501-510. Epub 2023 Sep 19 doi: 10.1007/s00280-023-04585-w. PMID: 37725113
Exceptional responses to PARP inhibitors in patients with metastatic breast cancer in oncologic crisis.
Cheng JM, Canzoniero J, Lee S, Soni S, Mangini N, Santa-Maria CA
Breast Cancer Res Treat 2023 Jun;199(2):389-397. Epub 2023 Mar 31 doi: 10.1007/s10549-023-06910-6. PMID: 37002487Free PMC Article
Survival outcomes in patients with BRCA mutated, variant of unknown significance, and wild type ovarian cancer treated with PARP inhibitors.
Musacchio L, Boccia S, Marchetti C, Minucci A, Camarda F, Cassani C, Ventriglia J, Salutari V, Ghizzoni V, Giudice E, Perri MT, Carbone MV, Ricci C, Pignata S, Fagotti A, Scambia G, Lorusso D
Int J Gynecol Cancer 2023 Jun 5;33(6):922-928. doi: 10.1136/ijgc-2022-003903. PMID: 36759000
BRCA1/2 Pathogenic Variants Are Not Common in Merkel Cell Carcinoma: Comprehensive Molecular Study of 30 Cases and Meta-Analysis of the Literature.
Gaubert A, Kervarrec T, Montaudié H, Burel-Vandenbos F, Cardot-Leccia N, Di Mauro I, Fabas T, Tallet A, Kubiniek V, Pedeutour F, Dadone-Montaudié B
J Invest Dermatol 2023 Jul;143(7):1178-1186. Epub 2023 Feb 7 doi: 10.1016/j.jid.2023.01.014. PMID: 36754117
Targeted molecular profiling of epithelial ovarian cancer from Italian BRCA wild-type patients with a BRCA and PARP pathways gene panel.
Salvati A, Carnevali I, Alexandrova E, Facchi S, Ronchi S, Libera L, Sahnane N, Memoli D, Lamberti J, Amabile S, Pepe S, Tarallo R, Sessa F, Weisz A, Tibiletti MG, Rizzo F
Exp Mol Pathol 2022 Oct;128:104833. Epub 2022 Sep 20 doi: 10.1016/j.yexmp.2022.104833. PMID: 36165864

Prognosis

Functional evaluation of BRCA1/2 variants of unknown significance with homologous recombination assay and integrative in silico prediction model.
Guo Q, Ji S, Takeuchi K, Urasaki W, Suzuki A, Iwasaki Y, Saito H, Xu Z, Arai M, Nakamura S, Momozawa Y, Chiba N, Miki Y, Matsuura M, Sunada S
J Hum Genet 2023 Dec;68(12):849-857. Epub 2023 Sep 20 doi: 10.1038/s10038-023-01194-6. PMID: 37731132
Treatment of women with BRCA mutation.
Depypere H
Climacteric 2023 Jun;26(3):235-239. Epub 2023 Apr 3 doi: 10.1080/13697137.2023.2189583. PMID: 37011662
Mutations of BRCA1/2 Genes in the West of Turkey and Genotype-Phenotype Correlations.
Gun-Bilgic D, Aydin-Gumus A, Bilgic A, Cam FS
Clin Lab 2022 Jan 1;68(1) doi: 10.7754/Clin.Lab.2021.210425. PMID: 35023674
Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants.
Houdayer C, Caux-Moncoutier V, Krieger S, Barrois M, Bonnet F, Bourdon V, Bronner M, Buisson M, Coulet F, Gaildrat P, Lefol C, Léone M, Mazoyer S, Muller D, Remenieras A, Révillion F, Rouleau E, Sokolowska J, Vert JP, Lidereau R, Soubrier F, Sobol H, Sevenet N, Bressac-de Paillerets B, Hardouin A, Tosi M, Sinilnikova OM, Stoppa-Lyonnet D
Hum Mutat 2012 Aug;33(8):1228-38. Epub 2012 May 11 doi: 10.1002/humu.22101. PMID: 22505045
A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes.
Easton DF, Deffenbaugh AM, Pruss D, Frye C, Wenstrup RJ, Allen-Brady K, Tavtigian SV, Monteiro AN, Iversen ES, Couch FJ, Goldgar DE
Am J Hum Genet 2007 Nov;81(5):873-83. Epub 2007 Sep 6 doi: 10.1086/521032. PMID: 17924331Free PMC Article

Clinical prediction guides

Functional evaluation of BRCA1/2 variants of unknown significance with homologous recombination assay and integrative in silico prediction model.
Guo Q, Ji S, Takeuchi K, Urasaki W, Suzuki A, Iwasaki Y, Saito H, Xu Z, Arai M, Nakamura S, Momozawa Y, Chiba N, Miki Y, Matsuura M, Sunada S
J Hum Genet 2023 Dec;68(12):849-857. Epub 2023 Sep 20 doi: 10.1038/s10038-023-01194-6. PMID: 37731132
Treatment of women with BRCA mutation.
Depypere H
Climacteric 2023 Jun;26(3):235-239. Epub 2023 Apr 3 doi: 10.1080/13697137.2023.2189583. PMID: 37011662
Mutations of BRCA1/2 Genes in the West of Turkey and Genotype-Phenotype Correlations.
Gun-Bilgic D, Aydin-Gumus A, Bilgic A, Cam FS
Clin Lab 2022 Jan 1;68(1) doi: 10.7754/Clin.Lab.2021.210425. PMID: 35023674
Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants.
Houdayer C, Caux-Moncoutier V, Krieger S, Barrois M, Bonnet F, Bourdon V, Bronner M, Buisson M, Coulet F, Gaildrat P, Lefol C, Léone M, Mazoyer S, Muller D, Remenieras A, Révillion F, Rouleau E, Sokolowska J, Vert JP, Lidereau R, Soubrier F, Sobol H, Sevenet N, Bressac-de Paillerets B, Hardouin A, Tosi M, Sinilnikova OM, Stoppa-Lyonnet D
Hum Mutat 2012 Aug;33(8):1228-38. Epub 2012 May 11 doi: 10.1002/humu.22101. PMID: 22505045
A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes.
Easton DF, Deffenbaugh AM, Pruss D, Frye C, Wenstrup RJ, Allen-Brady K, Tavtigian SV, Monteiro AN, Iversen ES, Couch FJ, Goldgar DE
Am J Hum Genet 2007 Nov;81(5):873-83. Epub 2007 Sep 6 doi: 10.1086/521032. PMID: 17924331Free PMC Article

Recent systematic reviews

BRCA1/BRCA2 mutation spectrum analysis in South Asia: a systematic review.
Kharel S, Shrestha S, Yadav S, Shakya P, Baidya S, Hirachan S
J Int Med Res 2022 Jan;50(1):3000605211070757. doi: 10.1177/03000605211070757. PMID: 35000471Free PMC Article

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