ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3627dupA (p.Glu1210Argfs) (rs80357729)

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Total submissions: 16
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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) RCV000031115 SCV000282312 pathogenic Breast-ovarian cancer, familial 1 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000048263 SCV000076276 pathogenic Hereditary breast and ovarian cancer syndrome 2019-12-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu1210Argfs*9) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant has been reported in the literature in numerous individuals affected with breast and/or ovarian cancer (PMID: 22798144, 22382806, 16949048, 22160602, 23633455). This variant is also known as 3627insA and 3746insA in the literature. ClinVar contains an entry for this variant (Variation ID: 37534). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000130022 SCV000184848 pathogenic Hereditary cancer-predisposing syndrome 2019-04-22 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Rarity in general population databases (dbsnp, esp, 1000 genomes)
GeneDx RCV000159919 SCV000210043 pathogenic Familial cancer of breast 2014-07-28 criteria provided, single submitter clinical testing This inserton of one nucleotide is denoted BRCA1 c.3627_3628insA (a.k.a c.3627dupA) at the cDNA level and p.Glu1210ArgfsX9 (E1210RfsX9) at the protein level. The normal sequence, with the base that is inserted in brackets, is ATTA{insA}GAGT. The insertion causes a frameshift, which changes a Glutamic Acid to an Arginine at codon 1210 in exon 10, and creates a premature stop codon at position 9 of the new reading frame. This mutation is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.3627_3628insA (a.k.a BRCA1 3627dupA), previously reported as 3746insA using alternate nomenclature, has observed in one Korean breast cancer patient (Kim 2006). We consider this mutation to be pathogenic and is indicative of Hereditary Breast and Ovarian Cancer (HBOC), an autosomal dominant condition that predisposes to early onset breast cancer, ovarian and fallopian tube cancer, as well as other cancers. Breast and ovarian cancer are the predominant BRCA1-related cancers that unaffected female mutation carriers are at risk to develop. The lifetime risk for breast cancer is estimated to be 57 to 84% and the lifetime risk for ovarian cancer is estimated to be 24 to 54% (Antoniou 2003, Chen 2007, Ford 1998). BRCA1 mutations have also been reported in women with fallopian tube carcinoma, primary peritoneal carcinoma, and uterine serous carcinoma (Levine 2003, Pennington 2013). Graeser et al. (2009) found that women who harbor a pathogenic BRCA1 mutation have an increased risk for contralateral breast cancer that is dependent on age at initial diagnosis. It is estimated that the risk to develop a second breast cancer within 10 years of the first diagnosis if initially diagnosed less than age 40 years of age is 31%, between the ages of 40 and 50 is 11% and after the age of 50 is 8%. Additionally, it is estimated that the risk to develop a second breast cancer within 25 years of their first diagnosis if initially diagnosed less than age 40 years of age is 63%, between the ages of 40 and 50 is 44% and after the age of 50 is 20%. Other cancer risks associated with a BRCA1 pathogenic variant include approximately a 20% risk for prostate cancer in male carriers (Thompson 2002), a 4% risk for male breast cancer (Liede 2004), and an estimated 1 to 3% risk for pancreatic cancer in both men and women (Brose 2002, Thompson 2002).The variant is found in BRCA1-BRCA2 panel(s).
Counsyl RCV000031115 SCV000221074 pathogenic Breast-ovarian cancer, familial 1 2015-01-23 criteria provided, single submitter literature only
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031115 SCV000325707 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000301326 SCV000329127 pathogenic not provided 2018-05-04 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA1 is denoted c.3627dupA at the cDNA level and p.Glu1210ArgfsX9 (E1210RfsX9) at the protein level. The normal sequence, with the base that is duplicated in brackets, is AATT[dupA]GAGT. The duplication causes a frameshift, which changes a Glutamic Acid to an Arginine at codon 1210, and creates a premature stop codon at position 9 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.3627dupA, previously reported as 3746insA using alternate nomenclature, has been observed in association with breast and/or ovarian cancer and is a recurrent variant in Korean populations (Kim 2006, Schneegans 2012, Kim 2012, Solano 2012, Hirasawa 2017). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000301326 SCV000600337 pathogenic not provided 2016-11-28 criteria provided, single submitter clinical testing
Color RCV000130022 SCV000683117 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000048263 SCV000699047 pathogenic Hereditary breast and ovarian cancer syndrome 2016-12-05 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3627dupA (p.Glu1210Argfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant of interest has not been observed in controls (ExAC, 1000 Gs, ESP, or publication controls) and has been reported in multiple affected individuals via publications. In addition, multiple databases and clinical diagnostic laboratories have cited the variant as "pathogenic." Therefore, the variant of interest has been classified as "Pathogenic."
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV000031115 SCV000839900 pathogenic Breast-ovarian cancer, familial 1 2017-05-25 criteria provided, single submitter clinical testing The c.3627dup (p.Glu1210Argfs*9) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 16949048, 23633455, 22160602]. This 1 bp duplication in exon 10 results in a frameshift and the creation of a premature stop codon. This variant is thus predicted to result in a loss of function of the protein. This variant has not been detected in the ExAC database. This variant thus classified as pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000301326 SCV001247354 pathogenic not provided 2017-04-01 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031115 SCV000053713 pathogenic Breast-ovarian cancer, familial 1 2012-02-14 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031115 SCV000144817 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048263 SCV000587322 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
3DMed Clinical Laboratory Inc RCV000677818 SCV000803978 pathogenic Ovarian Serous Surface Papillary Adenocarcinoma 2018-05-21 no assertion criteria provided clinical testing

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