ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.572_573AT[1] (p.Met192fs) (rs80359533)

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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506093 SCV000602885 pathogenic not specified 2017-04-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131852 SCV000186405 pathogenic Hereditary cancer-predisposing syndrome 2013-07-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131852 SCV000186907 pathogenic Hereditary cancer-predisposing syndrome 2015-01-31 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031574 SCV000147183 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131852 SCV000683730 pathogenic Hereditary cancer-predisposing syndrome 2016-07-30 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031574 SCV000327274 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031574 SCV000489153 pathogenic Breast-ovarian cancer, familial 2 2016-08-29 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031574 SCV000282414 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000235138 SCV000210703 pathogenic not provided 2018-08-10 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in BRCA2 is denoted c.574_575delAT at the cDNA level and p.Met192ValfsX13 (M192VfsX13) at the protein level. The normal sequence, with the bases that are deleted in brackets, is TGAT[delAT]GTCT. The deletion causes a frameshift, which changes a Methionine to a Valine at codon 192, and creates a premature stop codon at position 13 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.574_575delAT, also known as 802_803del, 802delAT, and 800delAT using alternate nomenclature, has been reported in association with breast and ovarian cancer (Evans 2003, Lalloo 2006, Safra 2013). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000044741 SCV000694898 pathogenic Hereditary breast and ovarian cancer syndrome 2016-01-22 criteria provided, single submitter clinical testing Variant summary: This c.574_575delAT variant causes a frameshift, which alters the proteins amino acid sequence beginning at position 192 and leads to a premature termination codon 12 amino acids downstream. It is predicted to cause a truncated or absent BRCA2 protein. Heterozygous loss-of-function due to mutations in this gene is an established disease mechanism in HBOC. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Asp252fs). This variant was not found in approximately 121394 chromosomes from the broad and large populations from ExAC. This variant has been reported in many HBOC patients/families from literature and databases. Multiple clinical laboratories and reputable databases have classified this variant as pathogenic. Taken together, this variant has currently been classified as a Pathogenic.
Invitae RCV000044741 SCV000072754 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Met192Valfs*13) 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 individuals affected with breast and/or ovarian cancer (PMID: 12960223, 26681312). This variant is also known as 800delAT and 802delAT in the literature. ClinVar contains an entry for this variant (Variation ID: 37993). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Michigan Medical Genetics Laboratories,University of Michigan RCV000031574 SCV000267733 pathogenic Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235138 SCV000296730 pathogenic not provided 2015-02-18 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044741 SCV000587556 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031574 SCV000054180 pathogenic Breast-ovarian cancer, familial 2 2013-07-05 no assertion criteria provided clinical testing

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