ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4471_4474del (p.Leu1491fs) (rs80359451)

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Total submissions: 7
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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) RCV000077326 SCV000300751 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 RCV000044419 SCV000072432 pathogenic Hereditary breast and ovarian cancer syndrome 2018-10-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu1491Lysfs*12) 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 several individuals affected with breast cancer (PMID: 24013928). This variant is also known as 4699del4 in the literature. ClinVar contains an entry for this variant (Variation ID: 51652). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000217416 SCV000277031 pathogenic Hereditary cancer-predisposing syndrome 2015-07-10 criteria provided, single submitter clinical testing
GeneDx RCV000484716 SCV000566376 pathogenic not provided 2015-04-23 criteria provided, single submitter clinical testing This deletion of 4 nucleotides in BRCA2 is denoted c.4471_4474delCTGA at the cDNA level and p.Leu1491LysfsX12 (L1491KfsX12) at the protein level. The normal sequence, with the bases that are deleted in braces, is AATA[CTGA]AAGA. The deletion causes a frameshift, which changes a Leucine to a Lysine at codon 1491, and creates a premature stop codon at position 12 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.4471_4474delCTGA, previously reported as BRCA2 4699del4, has been identified in at least 2 women with breast cancer (Pal 2014). We consider this mutation to be pathogenic
Color RCV000217416 SCV000683622 pathogenic Hereditary cancer-predisposing syndrome 2016-04-04 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077326 SCV000109123 pathogenic Breast-ovarian cancer, familial 2 2009-04-06 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077326 SCV000146427 pathogenic Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing

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