ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.729_732del (p.Asn243fs) (rs80359645)

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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 RCV000162898 SCV000213385 pathogenic Hereditary cancer-predisposing syndrome 2016-09-06 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) RCV000077400 SCV000147614 pathogenic Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077400 SCV000327629 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) RCV000077400 SCV000300351 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 RCV000482942 SCV000564761 pathogenic not provided 2018-09-13 criteria provided, single submitter clinical testing This deletion of four nucleotides in BRCA2 is denoted c.729_732delTGAT at the cDNA level and p.Asn243LysfsX7 (N243KfsX7) at the protein level. The normal sequence, with the bases that are deleted in braces, is GAAAAA[TGAT]AGAT. The deletion causes a frameshift which changes an Asparagine to a Lysine at codon 243, and creates a premature stop codon at position 7 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. Using alternate nomenclature, this variant has been defined as BRCA2 957del4 or 957_960delTGAT and has been reported in association with breast and/or ovarian cancer (Weitzel 2005). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000045180 SCV000695054 pathogenic Hereditary breast and ovarian cancer syndrome 2017-02-16 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.729_732delTGAT (p.Asn243Lysfs) 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.755_758delACAG (p.Asp252fs), c.771_775delTCAAA (p.Asn257fs), and c.778_779delGA (p.Glu260fs)). The variant of interest was not observed in controls (ExAC, 1000 Gs, or ESP). A publication cites the variant in an affected individual and the authors indicate that the variant is likely to be found in individuals of Hispanic origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as Pathogenic.
Invitae RCV000045180 SCV000073193 pathogenic Hereditary breast and ovarian cancer syndrome 2018-08-27 criteria provided, single submitter clinical testing This sequence change deletes 4 nucleotides in exon 9 of the BRCA2 mRNA (c.729_732delTGAT), causing a frameshift at codon 243. This creates a premature translational stop signal (p.Asn243Lysfs*7) 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 an individual with a personal and/or family history of breast and/or ovarian cancer (PMID: 16030099). This variant is also known as 957del4 in the literature. For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077400 SCV000296706 pathogenic Breast-ovarian cancer, familial 2 2015-03-18 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000482942 SCV000887911 pathogenic not provided 2015-03-18 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000045180 SCV000587565 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077400 SCV000109197 pathogenic Breast-ovarian cancer, familial 2 2009-03-31 no assertion criteria provided clinical testing

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