ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.18_19AG[2] (p.Arg8fs) (rs397507623)

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Total submissions: 6
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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) RCV000083090 SCV000300284 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Invitae RCV000043971 SCV000071984 pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg8Alafs*5) 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 observed in individuals with personal or family history of breast and/or ovarian cancer (PMID: 15131399, 22762150, 25330149, 25556971). This variant is also known as c.18_19delAG and 250delAG in the literature. ClinVar contains an entry for this variant (Variation ID: 51267). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000083090 SCV000296541 pathogenic Breast-ovarian cancer, familial 2 2016-04-04 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000083090 SCV000326667 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000043971 SCV000605788 pathogenic Hereditary breast and ovarian cancer syndrome 2016-08-05 criteria provided, single submitter clinical testing The p.Arg8fs variant in BRCA2 has been reported in 1 individual with a BRCA2-ass ociated cancer (Lubinski 2004) and was absent from large population studies, tho ugh the ability of these studies to accurately detect indels may be limited. Thi s variant is predicted to cause a frameshift, which alters the protein?s amino a cid sequence beginning at position 8 and leads to a premature termination codon 5 amino acids downstream. This alteration is then predicted to lead to a truncat ed or absent protein. Heterozygous loss of function of the BRCA2 gene is an esta blished disease mechanism in individuals with hereditary breast and ovarian canc er (HBOC). Furthermore, the p.Arg8fs variant was classified as Pathogenic on Sep tember 8, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar SCV000300284 .2). In summary, this variant meets our criteria to be classified as pathogenic for HBOC in an autosomal dominant manner based on predicted impact to the protei n and absence from controls.
Sharing Clinical Reports Project (SCRP) RCV000083090 SCV000115164 pathogenic Breast-ovarian cancer, familial 2 2011-12-15 no assertion criteria provided clinical testing

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