ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2517C>A (p.Tyr839Ter)

dbSNP: rs80358516
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Total submissions: 11
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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) RCV000113053 SCV000300526 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000131057 SCV000185987 pathogenic Hereditary cancer-predisposing syndrome 2022-11-29 criteria provided, single submitter clinical testing The p.Y839* pathogenic mutation (also known as c.2517C>A), located in coding exon 10 of the BRCA2 gene, results from a C to A substitution at nucleotide position 2517. This changes the amino acid from a tyrosine to a stop codon within coding exon 10. This alteration was identified twice in a large, worldwide study of BRCA1/2 mutation positive families (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.
GeneDx RCV000223462 SCV000279394 pathogenic not provided 2022-09-26 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in several families with Hereditary Breast and Ovarian Cancer syndrome (LaDuca et al., 2017; Rebbeck et al., 2018); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 2745C>A; This variant is associated with the following publications: (PMID: 28152038, 29446198, 32295079)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113053 SCV000326719 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2015-10-02 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000131057 SCV000906892 pathogenic Hereditary cancer-predisposing syndrome 2023-02-20 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 11 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been detected in families suspected of having hereditary breast and ovarian cancer (PMID: 28152038, 29446198). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001385315 SCV001585130 pathogenic Hereditary breast ovarian cancer syndrome 2023-09-01 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with increased risk of breast and/or ovarian cancer (PMID: 29446198). ClinVar contains an entry for this variant (Variation ID: 51299). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Tyr839*) 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).
Baylor Genetics RCV003473316 SCV004210426 pathogenic Familial cancer of breast 2023-11-14 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000223462 SCV004219546 pathogenic not provided 2023-01-31 criteria provided, single submitter clinical testing This nonsense variant causes the premature termination of BRCA2 protein synthesis. It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in high-risk breast and ovarian cancer families (PMID: 29446198 (2018)). Based on the available information, this variant is classified as pathogenic.
All of Us Research Program, National Institutes of Health RCV000113053 SCV004847064 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2023-12-13 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 11 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been detected in families suspected of having hereditary breast and ovarian cancer (PMID: 28152038, 29446198). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113053 SCV000146060 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2000-06-12 no assertion criteria provided clinical testing
CZECANCA consortium RCV001270986 SCV001451797 pathogenic Breast and/or ovarian cancer 2019-06-11 no assertion criteria provided clinical testing

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