ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.635_636del (p.Arg212fs) (rs80359575)

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Total submissions: 12
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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) RCV000076962 SCV000300340 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000076962 SCV000327399 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000483149 SCV000568451 pathogenic not provided 2018-08-03 criteria provided, single submitter clinical testing This deletion of two nucleotides in BRCA2 is denoted c.635_636delGA at the cDNA level and p.Arg212LysfsX2 (R212KfsX2) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 863_864delGA or 862delAG. The normal sequence, with the bases that are deleted in brackets, is GTCA[delGA]AATG. The deletion causes a frameshift which changes an Arginine to a Lysine at codon 212, and creates a premature stop codon at position 2 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.635_636delGA has been identified in multiple hereditary breast and/or ovarian cancer families (Verhoog 1999, Meindl 2002, Castera 2014). We consider this variant to be pathogenic.
Ambry Genetics RCV000510046 SCV000607925 pathogenic Hereditary cancer-predisposing syndrome 2017-10-09 criteria provided, single submitter clinical testing The c.635_636delGA pathogenic mutation, located in coding exon 7 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 635 to 636, causing a translational frameshift with a predicted alternate stop codon (p.R212Kfs*2). This mutation (designated as 862delAG) has been observed in families with Hereditary Breast and Ovarian Cancer (HBOC) syndrome (Verhoog LC et al. J. Clin. Oncol. 1999 Nov;17(11):3396-402; Meindl A. Int. J. Cancer. 2002 Feb;97(4):472-80). 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.
Color Health, Inc RCV000510046 SCV000688977 pathogenic Hereditary cancer-predisposing syndrome 2017-07-31 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000076962 SCV000744389 pathogenic Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000483149 SCV000887873 pathogenic not provided 2017-12-02 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000076962 SCV001428524 uncertain significance Breast-ovarian cancer, familial 2 2018-08-06 criteria provided, single submitter clinical testing
Invitae RCV001387343 SCV001587950 pathogenic Hereditary breast and ovarian cancer syndrome 2020-07-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg212Lysfs*2) 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 affected with breast and/or ovarian cancer (PMID: 10550133, 28324225, 29446198, 16683254). This variant is also known as 862delAG, and c.634_635delAG in the literature. ClinVar contains an entry for this variant (Variation ID: 91445). 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) RCV000076962 SCV000108759 pathogenic Breast-ovarian cancer, familial 2 2012-12-28 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000076962 SCV000147358 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000076962 SCV000733215 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing

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