ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3336del (p.Glu1113fs)

dbSNP: rs398122763
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Total submissions: 8
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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) RCV000077706 SCV000300621 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.
Michigan Medical Genetics Laboratories, University of Michigan RCV000077706 SCV000267757 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2016-04-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077706 SCV000296662 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2015-06-03 criteria provided, single submitter clinical testing
Counsyl RCV000077706 SCV000489566 likely pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2016-10-27 criteria provided, single submitter clinical testing
Invitae RCV001232803 SCV001405372 pathogenic Hereditary breast ovarian cancer syndrome 2023-04-06 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 91798). This premature translational stop signal has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 21520333). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu1113Asnfs*6) 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 RCV003343632 SCV004052503 pathogenic Hereditary cancer-predisposing syndrome 2023-06-27 criteria provided, single submitter clinical testing The c.3336delA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 3336, causing a translational frameshift with a predicted alternate stop codon (p.E1113Nfs*6). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001232803 SCV004122588 pathogenic Hereditary breast ovarian cancer syndrome 2023-10-09 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3336delA (p.Glu1113AsnfsX6) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant was absent in 238638 control chromosomes. To our knowledge, no occurrence of c.3336delA in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000077706 SCV000109509 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2007-06-11 no assertion criteria provided clinical testing

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