ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3048_3052dupTGAGA (p.Asn1018Metfs) (rs80357856)

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Total submissions: 14
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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) RCV000019262 SCV000323556 pathogenic Breast-ovarian cancer, familial 1 2016-10-18 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000048059 SCV000076072 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn1018Metfs*8) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. While this variant is present in population databases (rs80357856), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported as the most common cause of breast and ovarian cancer in the Western Swedish population (PMID: 11781691, 15951958, 20151938), although it has also been reported in other ethnicities (PMID: 24504028). This variant is also known as 3171ins5 in the literature. ClinVar contains an entry for this variant (Variation ID: 54763). This variant has been associated with a 59-93% risk of breast or ovarian cancer by age 70 (PMID: 11576847). 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 RCV000131332 SCV000186306 pathogenic Hereditary cancer-predisposing syndrome 2017-12-01 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)
GeneDx RCV000159913 SCV000210033 pathogenic not provided 2017-06-30 criteria provided, single submitter clinical testing This duplication of 5 nucleotides is denoted BRCA1 c.3048_3052dupTGAGA at the cDNA level and p.Asn1018MetfsX8 (N1018MfsX8) at the protein level. The normal sequence, with the bases that are duplicated in braces, is GAAA[TGAGA]ACAT. The duplication causes a frameshift, which changes an Asparagine to a Methionine at codon 1018, and creates a premature stop codon at position 8 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.3048_3052dupTGAGA, previously reported as 3171ins5 or 3166ins5, using alternate nomenclature has been observed in multiple families with breast, ovarian and pancreatic cancers and is the most common Swedish founder variant (Shattuck-Eidens 1995, Johannsson 1996, Bergman 2001, Cunningham 2014). We consider this variant to be pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000019262 SCV000296295 pathogenic Breast-ovarian cancer, familial 1 2015-02-12 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000019262 SCV000325544 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics,Oslo University Hospital RCV000019262 SCV000564330 pathogenic Breast-ovarian cancer, familial 1 2015-07-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000048059 SCV000591422 pathogenic Hereditary breast and ovarian cancer syndrome 2015-10-22 criteria provided, single submitter clinical testing
Color RCV000131332 SCV000683084 pathogenic Hereditary cancer-predisposing syndrome 2015-06-08 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000159913 SCV000887657 pathogenic not provided 2015-02-12 criteria provided, single submitter clinical testing
OMIM RCV000019262 SCV000039550 pathogenic Breast-ovarian cancer, familial 1 2001-10-01 no assertion criteria provided literature only
Breast Cancer Information Core (BIC) (BRCA1) RCV000019262 SCV000144624 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Pathway Genomics RCV000019262 SCV000189891 pathogenic Breast-ovarian cancer, familial 1 2014-07-24 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000048059 SCV000587274 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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