ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2125_2126insA (p.Phe709fs) (rs80357871)

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Total submissions: 9
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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) RCV000083179 SCV000299702 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000047722 SCV000075735 pathogenic Hereditary breast and ovarian cancer syndrome 2017-06-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Phe709Tyrfs*3) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with breast and ovarian cancer (PMID: 10200350, 16905680, 24549055, 25884701, 27083178). This variant is also known as 2244insA in the literature. ClinVar contains an entry for this variant (Variation ID: 54469). Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Michigan Medical Genetics Laboratories,University of Michigan RCV000083179 SCV000195901 pathogenic Breast-ovarian cancer, familial 1 2014-11-03 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000083179 SCV000325244 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000483700 SCV000566679 pathogenic not provided 2018-09-14 criteria provided, single submitter clinical testing This insertion of one nucleotide in BRCA1 is denoted c.2125_2126insA at the cDNA level and p.Phe709TyrfsX3 (F709YfsX3) at the protein level. The normal sequence, with the base that is inserted in brackets, is TCTT[insA]TTAC. The insertion causes a frameshift, which changes a Phenylalanine to a Tyrosine at codon 709, and creates a premature stop codon at position 3 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.2125_2126insA, previously reported as 2244insA, has been identified in association with breast and ovarian cancer (Laplace-Marieze 1999, Simard 2007, Belanger 2015, Jouali 2016) and is considered pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000083179 SCV000115253 pathogenic Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083179 SCV000144308 pathogenic Breast-ovarian cancer, familial 1 2004-11-25 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000047722 SCV000587185 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735501 SCV000863639 pathogenic Breast and/or ovarian cancer 2012-03-27 no assertion criteria provided clinical testing

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