ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6611del (p.Pro2204fs)

dbSNP: rs1135401915
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001801165 SCV002046156 pathogenic not provided 2021-04-13 criteria provided, single submitter clinical testing This frameshift variant causes the premature termination of BRCA2 protein synthesis. It has been reported in multiple individuals and families affected with breast cancer in the published literature (PMID: 29907814 (2018), 27741520 (2016), and 23320992 (2013)). This variant has not been reported in large, multi-ethnic general populations. Based on the available information, this variant is classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001869456 SCV002237272 pathogenic Hereditary breast ovarian cancer syndrome 2023-05-21 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). ClinVar contains an entry for this variant (Variation ID: 1330148). This variant is also known as 6839delC. This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 23320992, 29907814). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro2204Leufs*2) 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).
Ambry Genetics RCV004946743 SCV005548635 pathogenic Hereditary cancer-predisposing syndrome 2024-07-06 criteria provided, single submitter clinical testing The c.6611delC pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 6611, causing a translational frameshift with a predicted alternate stop codon (p.P2204Lfs*2). This alteration has been identified in multiple individuals diagnosed with breast cancer (Pal T et al. Breast J, 2013 Jan;19:189-92; Fernandes GC et al. Oncotarget, 2016 Dec;7:80465-80481). Of note, this alteration is also known as 6839delC in published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Fulgent Genetics, Fulgent Genetics RCV005006060 SCV005633959 pathogenic Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3; Familial prostate cancer 2023-12-28 criteria provided, single submitter clinical testing

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