ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7024C>T (p.Gln2342Ter) (rs80358928)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077396 SCV000301121 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000215667 SCV000273810 pathogenic Hereditary cancer-predisposing syndrome 2018-12-27 criteria provided, single submitter clinical testing The p.Q2342* pathogenic mutation (also known as c.7024C>T), located in coding exon 13 of the BRCA2 gene, results from a C to T substitution at nucleotide position 7024. This changes the amino acid from a glutamine to a stop codon within coding exon 13. This alteration has been previously identified in several European and North American breast/ovarian cohorts, as well as in an individual with male breast and prostate cancer (Panchal S et al. Nat Rev Clin Oncol. 2009 Oct;6:604-7; Grindedal EM et al. BMC Cancer. 2017 Jun;17(1):438; Rebbeck TR et al. Hum. Mutat. 2018 May;39(5):593-620). Of note, this alteration is also designated 7252C>T in the published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077396 SCV000296617 pathogenic Breast-ovarian cancer, familial 2 2015-09-22 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077396 SCV000327580 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Department of Medical Genetics, Oslo University Hospital RCV000077396 SCV000605672 pathogenic Breast-ovarian cancer, familial 2 2015-07-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV000215667 SCV000683844 pathogenic Hereditary cancer-predisposing syndrome 2020-02-28 criteria provided, single submitter clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000077396 SCV000778598 likely pathogenic Breast-ovarian cancer, familial 2 2018-01-23 criteria provided, single submitter research
Counsyl RCV000077396 SCV000785707 pathogenic Breast-ovarian cancer, familial 2 2017-11-08 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000681960 SCV000889122 pathogenic not provided 2019-12-09 criteria provided, single submitter clinical testing The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and found in general population data at a frequency that is consistent with pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000496229 SCV000919013 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-12 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.7024C>T (p.Gln2342X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. p.Arg2394X, p.Ile2454fsX13, p.Asn2460fsX15). 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.1e-06 in 246056 control chromosomes. c.7024C>T has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Couch_2015, Grindedal_2017, Panchal_2009). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV000077396 SCV001434855 pathogenic Breast-ovarian cancer, familial 2 2018-10-12 criteria provided, single submitter clinical testing This rare nonsense variant c.7024C>T, (p.Gln2342Ter) in the BRCA2 gene is rare in public databases (seen once in Gnomad) and is predicted to result in a loss of function of BRCA2. Loss of function variants in BRCA1 are known to be pathogenic for breast cancer. This variant has been observed in multiple unrelated individuals with breast and other cancers (PMID 11836363, 12491487, 19787003). Family history was consistent with mode of iheritance of breast cancer in one family (PMID 19787003). Based upon the above evidence, this c.7024C>T, (p.Gln2342*) variant in BRCA2 is classified as pathogenic.
Invitae RCV000496229 SCV001590146 pathogenic Hereditary breast and ovarian cancer syndrome 2020-10-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln2342*) 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 cancer and prostate cancer (PMID: 28637432, 19787003). ClinVar contains an entry for this variant (Variation ID: 52250). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077396 SCV000109193 pathogenic Breast-ovarian cancer, familial 2 2013-11-07 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077396 SCV000147003 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000496229 SCV000587881 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Gharavi Laboratory,Columbia University RCV000681960 SCV000809455 pathogenic not provided 2018-09-16 no assertion criteria provided research

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