ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4554del (p.Glu1518fs) (rs80359458)

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Total submissions: 11
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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) RCV000113319 SCV000300765 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113319 SCV000327053 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000113319 SCV000677679 likely pathogenic Breast-ovarian cancer, familial 2 2016-11-22 criteria provided, single submitter clinical testing
Color Health, Inc RCV000581479 SCV000688881 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000496545 SCV000694779 pathogenic Hereditary breast and ovarian cancer syndrome 2016-03-09 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.4554delA variant results in a premature termination codon at codon 1542, predicted to cause a truncated or absent BRCA2 protein due to non-sense mediated decay, which are commonly known mechanisms for HBOC. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Tyr3308X, p.Ser3147fs). Mutation Taster predicts a damaging outcome for this variant. This variant was not found in 120318 control chromosomes, but was identified in multiple breast cancer patients in the literature. In addition, several clinical laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant was classified as pathogenic.
Ambry Genetics RCV000581479 SCV001184455 pathogenic Hereditary cancer-predisposing syndrome 2019-04-17 criteria provided, single submitter clinical testing The c.4554delA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 4554, causing a translational frameshift with a predicted alternate stop codon (p.E1518Dfs*25). This alteration was detected in 1/989 unrelated individuals from a cohort of German breast/ovarian cancer families (Meindl A et al. Int. J. Cancer, 2002 Feb;97:472-80). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001091963 SCV001248274 pathogenic not provided 2019-08-01 criteria provided, single submitter clinical testing
Invitae RCV000496545 SCV001580395 pathogenic Hereditary breast and ovarian cancer syndrome 2020-10-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu1518Aspfs*25) in the BRCA2 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 a family and an individual affected with breast cancer (PMID: 22160602, 11802209). This variant is also known as 4782delA, 4781delA in the literature. ClinVar contains an entry for this variant (Variation ID: 66339). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113319 SCV000146446 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000113319 SCV000297527 pathogenic Breast-ovarian cancer, familial 2 2010-05-27 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496545 SCV000587716 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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