ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6024dupG (p.Gln2009Alafs) (rs80359554)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131918 SCV000186973 pathogenic Hereditary cancer-predisposing syndrome 2017-10-18 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) RCV000031596 SCV000146751 pathogenic Breast-ovarian cancer, familial 2 2002-06-20 no assertion criteria provided clinical testing
Color RCV000131918 SCV000292137 pathogenic Hereditary cancer-predisposing syndrome 2016-08-25 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031596 SCV000327332 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000044820 SCV000592021 pathogenic Hereditary breast and ovarian cancer syndrome 2015-12-17 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031596 SCV000300969 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 RCV000390850 SCV000329594 pathogenic not provided 2018-06-04 criteria provided, single submitter clinical testing This duplication of one nucleotide in BRCA2 is denoted c.6024dupG at the cDNA level and p.Gln2009AlafsX9 (Q2009AfsX9) at the protein level. The normal sequence, with the base that is duplicated in brackets, is CCAA[dupG]CAAG. The duplication causes a frameshift, which changes a Glutamine to an Alanine at codon 2009, and creates a premature stop codon at position 9 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.6024dupG, previously published as BRCA2 6252dupG, has been observed in association with Hereditary Breast and Ovarian Cancer syndrome (Salgado 2005, Rodr?guez 2012, Yablonski-Peretz 2016, Torres 2017). We consider this variant to be pathogenic.
Genologica Medica RCV000031596 SCV000577960 pathogenic Breast-ovarian cancer, familial 2 2017-01-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000044820 SCV000919039 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-17 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.6024dupG (p.Gln2009AlafsX9) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4.1e-06 in 245708 control chromosomes (gnomAD). c.6024dupG has been reported in the literature in multiple individuals affected with Breast and/or Ovarian Cancer (Cardoso_2018, Pajares_2018, Villareal-Garza_2015, Chaudhury_2013, Rodriguez_2012, Salgado_2005, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. Ten ClinVar submissions from clinical diagnostic laboratories and reputable databases (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000044820 SCV000072833 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln2009Alafs*9) 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 with breast and ovarian cancer (PMID: 15944772, 22044689, 25236687, 26687385). This variant is also known as 6252insG in the literature. ClinVar contains an entry for this variant (Variation ID: 38015). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000044820 SCV000838827 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000390850 SCV000296610 pathogenic not provided 2015-09-29 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031596 SCV000054203 pathogenic Breast-ovarian cancer, familial 2 2012-09-27 no assertion criteria provided clinical testing

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