ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6535_6536insA (p.Val2179fs)

dbSNP: rs80359601
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Total submissions: 10
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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) RCV000031632 SCV000282429 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031632 SCV000327456 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2015-10-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759643 SCV000889102 pathogenic not provided 2023-01-19 criteria provided, single submitter clinical testing This frameshift variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. The frequency of this variant in the general population, 0.0000041 (1/243430 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been reported in individuals with ovarian cancer (PMID: 34657373 (2022)), bladder cancer (PMID: 29909963 (2018)), and colorectal cancer (PMID: 27356891 (2016)). It has also been reported in world-wide screen of BRCA1/BRCA2 mutation carriers (PMID: 29446198 (2018)). Based on the available information, this variant is classified as pathogenic.
Academic Department of Medical Genetics, University of Cambridge RCV000850059 SCV000992215 likely pathogenic Hereditary cancer-predisposing syndrome 2018-01-26 criteria provided, single submitter research Application of AMCG guidelines 2015. Used other ClinVar submission evidence where relevant. Loss of heterozygosity in tumours or immunohistochemistry abnormalities considered functional evidence of pathogenicity.
Ambry Genetics RCV000850059 SCV001187558 pathogenic Hereditary cancer-predisposing syndrome 2021-07-13 criteria provided, single submitter clinical testing The c.6535_6536insA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from an insertion of one nucleotide at position 6535, causing a translational frameshift with a predicted alternate stop codon (p.V2179Dfs*10). This variant has been identified multiple breast/ovarian cancer families (Palma MD et al. Cancer Res, 2008 Sep;68:7006-14; Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620). 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.
Invitae RCV000496438 SCV001578509 pathogenic Hereditary breast ovarian cancer syndrome 2023-12-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val2179Aspfs*10) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80359601, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer and colorectal cancer (PMID: 18703817, 27356891, 29371908, 29446198). This variant is also known as 6763insA. ClinVar contains an entry for this variant (Variation ID: 38050). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003460522 SCV004216091 pathogenic Familial cancer of breast 2023-06-06 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031632 SCV000054239 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2009-04-15 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031632 SCV000146880 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto RCV000496438 SCV000587856 pathogenic Hereditary breast ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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