ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2957_2958insG (p.Asn986fs) (rs1555282969)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131097 SCV000186027 pathogenic Hereditary cancer-predisposing syndrome 2016-05-17 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) RCV000031392 SCV000146149 pathogenic Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing
Color RCV000131097 SCV000688780 pathogenic Hereditary cancer-predisposing syndrome 2017-07-31 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031392 SCV000326790 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031392 SCV000677674 pathogenic Breast-ovarian cancer, familial 2 2017-05-09 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031392 SCV000300576 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 RCV000482218 SCV000569916 pathogenic not provided 2016-04-12 criteria provided, single submitter clinical testing This insertion of one nucleotide in BRCA2 is denoted c.2957_2958insG at the cDNA level and p.Asn986LysfsX2 (N986KfsX2) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 3185insG. The normal sequence, with the base that is inserted in braces, is GAAAAAAA[G]TAAT. The insertion causes a frameshift which changes an Asparagine to a Lysine at codon 986, and creates a premature stop codon at position 2 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.2957_2958insG has been observed in one individual with a history of breast and pancreatic cancer (Holter 2015). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000463291 SCV000694655 pathogenic Hereditary breast and ovarian cancer syndrome 2016-12-08 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.2957_2958insG (p.Asn986Lysfs) 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. Another variant at this position, c.2957dupA that causes the same frameshift mutation has been cited and classified as "pathogenic." The variant of interest has not been observed in controls (ExAC, 1000 Gs, or ESP) and has been reported in multiple affected individuals via publications. In addition, multiple clinical diagnostic laboratories/databases cite the variant as "pathogenic." Therefore, the variant of interest has been classified as "pathogenic."
Invitae RCV000463291 SCV000549846 pathogenic Hereditary breast and ovarian cancer syndrome 2018-08-01 criteria provided, single submitter clinical testing This sequence change inserts 1 nucleotide in exon 11 of the BRCA2 mRNA (c.2957_2958insG), causing a frameshift at codon 986. This creates a premature translational stop signal (p.Asn986Lysfs*2) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic. This particular variant has been reported in the literature in an individual affected with breast and pancreatic cancer (PMID: 25940717, 26219728). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000482218 SCV000600536 pathogenic not provided 2016-10-01 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031392 SCV000053997 pathogenic Breast-ovarian cancer, familial 2 2011-03-24 no assertion criteria provided clinical testing

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