ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5112_5115AATA[1] (p.Asn1706fs) (rs276174853)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077344 SCV000300829 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000131076 SCV000186006 pathogenic Hereditary cancer-predisposing syndrome 2017-08-11 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077344 SCV000296607 pathogenic Breast-ovarian cancer, familial 2 2015-09-19 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077344 SCV000327134 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000496624 SCV000591942 pathogenic Hereditary breast and ovarian cancer syndrome 2014-02-18 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758904 SCV000887838 pathogenic not provided 2015-09-19 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077344 SCV000109141 pathogenic Breast-ovarian cancer, familial 2 2010-03-29 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077344 SCV000146541 pathogenic Breast-ovarian cancer, familial 2 2007-02-14 no assertion criteria provided clinical testing
GeneDx RCV000044561 SCV000210811 pathogenic Familial cancer of breast 2013-11-01 no assertion criteria provided clinical testing This variant is denoted BRCA2 c.5116_5119delAATA at the cDNA level and p.Asn1706LeufsX5 (N1706LfsX5) at the protein level according to current HGVS nomenclature guidelines and is also known as c.5344_5347delAATA using alternative nomenclature. The surrounding sequence is GAATA{delAATA}CTGC. The deletion causes a frameshift, changing an Asparagine to a Leucine at codon 1706, and creating a premature stop codon at position 5 of the new reading frame. BRCA2 c.5116_5119delAATA is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This deletion has been reported as a pathogenic variant in an individual with early onset breast cancer and another with familial breast and ovarian cancer (Infante 2006), and is indicative of Hereditary Breast and Ovarian Cancer (HBOC) syndrome, an autosomal dominant condition that predisposes to breast and ovarian cancer as well as other cancers. The predominant BRCA2-related cancer risks for women who have not been diagnosed with cancer have been estimated as 41% - 84% lifetime risk for breast cancer and 11% - 27% lifetime risk for ovarian cancer (Ford 1998, Risch 2006). BRCA2 variants have also been reported in women with fallopian tube carcinoma, primary peritoneal carcinoma, and uterine serous carcinoma (Levine 2003, Biron-Shental 2006). Women with BRCA1/2 variants also have an increased risk for contralateral breast cancer. Women with BRCA variants whose first cancer was diagnosed under age 40 have a 21-31% risk to develop a second breast cancer within 10 years and a 63% risk to develop a second breast cancer within 25 years. Women with BRCA variants whose first cancer was diagnosed between ages 40 and 50 have an 11-13% risk to develop a second breast cancer within 10 years and a 44-49% risk within 25 years. Women with BRCA variants whose first cancer was diagnosed after age 50 have an 8% risk to develop a second breast cancer within 10 years and a 20% risk within 25 years (Graeser 2009). Other cancer risks associated with a BRCA2 variant include up to a 7% risk for pancreatic cancer (Ozcelik 1997, The Breast Cancer Linkage Consortium 1999), up to a 34% risk for prostate cancer in male carriers (Thompson 2001), and up to a 7% risk for male breast cancer (Liede 2004). Fanconi Anemia (FA) is a rare autosomal recessive condition that can be caused by two variants (one from each parent) in the BRCA2 gene. This condition is characterized by an increased risk for malignancy in children including leukemia and certain solid tumors as well as physical abnormalities and bone marrow failure. If a BRCA2 variant carrier’s partner is also heterozygous for a BRCA2 variant, the risk to have a child with FA is 25% with each pregnancy. The variant is found in BRCA2 panel(s).
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496624 SCV000587745 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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