ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6333_6337del (p.Arg2112fs) (rs397507369)

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Total submissions: 5
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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) RCV000031620 SCV000301019 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000213663 SCV000279400 pathogenic not provided 2016-11-03 criteria provided, single submitter clinical testing This deletion of 5 nucleotides in BRCA2 is denoted c.6333_6337delGAGAA at the cDNA level and p.Arg2112ProfsX15 (R2112PfsX15) at the protein level. The normal sequence, with the bases that are deleted in braces, is ATAA[GAGAA]ACCC. The deletion causes a frameshift, which changes an Arginine to a Proline at codon 2112, and creates a premature stop codon at position 15 of the new reading frame. Using alternate nomenclature, this variant would be defined as BRCA2 6561_6565delGAGAA or 6561del5. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.6333_6337delGAGAA has been reported in association with breast cancer (Suter 2004). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000588371 SCV000694966 pathogenic Hereditary breast and ovarian cancer syndrome 2016-08-01 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.6333_6337delGAGAA (p.Arg2112Profs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant is absent in 120468 control chromosomes while it was observe in a breast cancer patient indicating pathogenicity. Moreover, truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Glu3111X, p.Leu3135fs) further supporting a deleterious outcome. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as Pathogenic. Taken together, this variant is classified as Pathogenic.
Invitae RCV000588371 SCV000814483 pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2112Profs*15) 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 reported in an individual affected with breast cancer (PMID: 14973102). This variant is also known as 6561del5. ClinVar contains an entry for this variant (Variation ID: 38038). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000031620 SCV000054227 pathogenic Breast-ovarian cancer, familial 2 2011-04-18 no assertion criteria provided clinical testing

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