ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9027del (p.His3010fs) (rs80359742)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000572265 SCV000661276 pathogenic Hereditary cancer-predisposing syndrome 2017-08-22 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) RCV000114033 SCV000147517 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000114033 SCV000328031 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000114033 SCV000301337 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000522880 SCV000617476 pathogenic not provided 2017-03-29 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.9027delT at the cDNA level and p.His3010IlefsX18 (H3010IfsX18) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 c.9255delT. The normal sequence, with the base that is deleted in brackets, is TTTA[delT]CATC. The deletion causes a frameshift which changes a Histidine to an Isoleucine at codon 3010, and creates a premature stop codon at position 18 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.9027delT has been observed in individuals with a personal history of breast cancer and a family history of breast and/or ovarian cancer (Manguoglu 2003, Tea 2014, Wojcik 2016). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000779982 SCV000916962 pathogenic Hereditary breast and ovarian cancer syndrome 2017-11-03 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.9027delT (p.His3010IlefsX18) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.9076C>T (p.Gln3026X), c.9093_9094delinsG (p.Thr3033fsX29), c.9097dupA (p.Thr3033fsX11)). The variant has been reported in multiple HBOC affected individuals in literature (Manguoglu 2003, Tea 2014, Wojcik 2016). This variant is absent in 245484 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.

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