ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7556dup (p.Arg2520fs) (rs80359660)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215159 SCV000277909 pathogenic Hereditary cancer-predisposing syndrome 2015-08-20 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000076999 SCV000147120 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000215159 SCV000905182 pathogenic Hereditary cancer-predisposing syndrome 2017-11-30 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000076999 SCV000301177 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 RCV000520026 SCV000618303 pathogenic not provided 2018-05-03 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA2 is denoted c.7556dupC at the cDNA level and p.Arg2520SerfsX19 (R2520SfsX19) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 7784insC. The normal sequence, with the base that is duplicated in brackets, is CTGC[dupC]TCGA. The duplication causes a frameshift which changes an Arginine to a Serine at codon 2520, and creates a premature stop codon at position 19 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. This variant has been observed in at least one hereditary breast cancer family (Rodriguez 2008). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000540441 SCV000695077 pathogenic Hereditary breast and ovarian cancer syndrome 2016-07-26 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.7556dupC (p.Arg2520Serfs) 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. One in silico tool predicts a damaging outcome for this variant. This variant is absent in 120750 control chromosomes while it was reported in one HBOC family indicating pathogenicity. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Arg2520X, p.Trp2574fs) further supporting a deleterious outcome. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as Pathogenic. Taken together, this variant is classified as Pathogenic.
Invitae RCV000540441 SCV000635583 pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-18 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 15 of the BRCA2 mRNA (c.7556dupC), causing a frameshift at codon 2520. This creates a premature translational stop signal (p.Arg2520Serfs*19) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, 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 RCV000520026 SCV000889132 pathogenic not provided 2018-05-18 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000076999 SCV000108796 pathogenic Breast-ovarian cancer, familial 2 2006-08-03 no assertion criteria provided clinical testing

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