ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6944_6947del (p.Ile2315fs) (rs80359629)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131028 SCV000185958 pathogenic Hereditary cancer-predisposing syndrome 2017-11-09 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)
Breast Cancer Information Core (BIC) (BRCA2) RCV000031657 SCV000146977 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131028 SCV000911168 pathogenic Hereditary cancer-predisposing syndrome 2017-10-20 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031657 SCV000327545 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031657 SCV000220716 likely pathogenic Breast-ovarian cancer, familial 2 2014-09-22 criteria provided, single submitter literature only
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031657 SCV000282437 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000212255 SCV000210785 pathogenic not provided 2017-03-17 criteria provided, single submitter clinical testing This deletion of four nucleotides in BRCA2 is denoted c.6944_6947delTAAA at the cDNA level and p.Ile2315LysfsX12 (I2315KfsX12) at the protein level. The normal sequence, with the bases that are deleted in brackets, is ACAA[delTAAA]AGAT. The deletion causes a frameshift which changes an Isoleucine to a Lysine at codon 2315, and creates a premature stop codon at position 12 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. BRCA2 c.6944_6947delTAAA, previously reported as 7172del4 and 7172delTAAA using alternate nomenclature, has been reported in at least three families with early-onset breast cancer, ovarian cancer, and/or male breast cancer (Frank 1998, Evans 2008, Wong-Brown 2015) and is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000045094 SCV000695012 pathogenic Hereditary breast and ovarian cancer syndrome 2016-03-25 criteria provided, single submitter clinical testing Variant Summary: This frameshift variant is predicted to alter the 3418 amino acid long BRCA2 protein beginning at position 2315 leading to premature termination codon 12 amino acids downstream. It likely results in a loss of normal protein function due to production of a truncated protein or by the absence of the protein product due to nonsense-mediated mRNA decay. Mutation Taster predicts the variant of interest to be "disease-causing." The variant vas observed at a very low allele frequency in the large cohort of ExAC project while it was reported in multiple HBOC patients indicating the variant to be disease causing. Additionally, clinical diagnostic centers via ClinVar and reputable databases classify variant as Pathogenic. Considering all evidence, the variant is classified as a Pathogenic.
Invitae RCV000045094 SCV000073107 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile2315Lysfs*12) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs751065688, ExAC 0.003%). This variant has been reported in the literature in individuals affected with breast cancer (PMID: 9667259, 25682074). This variant is also known as 7172del4 in the literature. ClinVar contains an entry for this variant (Variation ID: 38075). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212255 SCV000296546 pathogenic not provided 2016-04-08 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000045094 SCV000587871 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031657 SCV000054264 pathogenic Breast-ovarian cancer, familial 2 2012-02-29 no assertion criteria provided clinical testing

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