ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5631del (p.Asn1877fs) (rs397507357)

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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) RCV000031562 SCV000300909 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics RCV000166635 SCV000217439 pathogenic Hereditary cancer-predisposing syndrome 2018-09-27 criteria provided, single submitter clinical testing The c.5631delC pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 5631, causing a translational frameshift with a predicted alternate stop codon (p.N1877Kfs*32). In a study of 810 unselected women with breast cancer from Mexico, this mutation (designated as 5859delC) was identified in a 56-year-old female with DCIS (Torres-Mejía G et al. Cancer Epidemiol. Biomarkers Prev. 2015 Mar;24(3):498-505). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000505842 SCV000296614 pathogenic not provided 2015-11-18 criteria provided, single submitter clinical testing
Counsyl RCV000031562 SCV000488147 likely pathogenic Breast-ovarian cancer, familial 2 2016-02-19 criteria provided, single submitter clinical testing
Color Health, Inc RCV000166635 SCV000688935 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
GeneDx RCV000505842 SCV000778883 pathogenic not provided 2018-05-01 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.5631delC at the cDNA level and p.Asn1877LysfsX32 (N1877KfsX32) at the protein level. The normal sequence, with the base that is deleted in brackets, is GAAAA[delC]AACG. The deletion causes a frameshift which changes an Asparagine to a Lysine at codon 1877, and creates a premature stop codon at position 32 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.5631delC, previously reported as 5859delC, has been observed in a woman with a personal history of breast cancer (Torres-Mejia 2015) . We consider this variant to be pathogenic.
Invitae RCV001044806 SCV001208624 pathogenic Hereditary breast and ovarian cancer syndrome 2020-09-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn1877Lysfs*32) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs397507357, ExAC 0.009%). This variant has been observed in an individual affected with breast cancer (PMID: 25371446). This variant is also known as c.5859delC in the literature. ClinVar contains an entry for this variant (Variation ID: 37981). 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) RCV000031562 SCV000054167 pathogenic Breast-ovarian cancer, familial 2 2010-09-14 no assertion criteria provided clinical testing

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