ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6643del (p.Tyr2215fs) (rs80359614)

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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 RCV000574731 SCV000668695 pathogenic Hereditary cancer-predisposing syndrome 2016-08-04 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) RCV000077380 SCV000146898 pathogenic Breast-ovarian cancer, familial 2 2000-08-16 no assertion criteria provided clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000735589 SCV000901118 pathogenic Breast and/or ovarian cancer 2017-09-08 criteria provided, single submitter clinical testing
Color RCV000574731 SCV000683793 pathogenic Hereditary cancer-predisposing syndrome 2017-04-10 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077380 SCV000327482 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000496286 SCV000592067 pathogenic Hereditary breast and ovarian cancer syndrome 2013-11-08 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077380 SCV000301082 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735589 SCV000863727 pathogenic Breast and/or ovarian cancer 2013-12-11 no assertion criteria provided clinical testing
GeneDx RCV000486817 SCV000565684 pathogenic not provided 2018-01-26 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.6643delT at the cDNA level and p.Tyr2215ThrfsX14 (Y2215TfsX14) at the protein level. The normal sequence, with the base that is deleted in braces, is TACT[T]ACTC. The deletion causes a frameshift which changes a Tyrosine to a Threonine at codon 2215, and creates a premature stop codon at position 14 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.6643delT, also known as 6871delT and 6870delT using alternate nomenclature, has been identified in at least two Hereditary Breast and Ovarian Cancer families (Lubinski 2004, Holter 2015). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000496286 SCV000917024 pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-17 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.6643delT (p.Tyr2215ThrfsX14) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4.1e-06 in 244376 control chromosomes (gnomAD). c.6643delT has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Holter_2015, Lubinski_2004, Rebbeck_2018). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496286 SCV000587861 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077380 SCV000109177 pathogenic Breast-ovarian cancer, familial 2 2012-09-28 no assertion criteria provided clinical testing

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