ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4947_4948del (p.Pro1651fs) (rs80359474)

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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) RCV000113361 SCV000300806 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 RCV000044529 SCV000072542 pathogenic Hereditary breast and ovarian cancer syndrome 2018-05-08 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides from exon 11 of the BRCA2 mRNA (c.4947_4948delAA), causing a frameshift at codon 1651. This creates a premature translational stop signal (p.Pro1651Cysfs*14) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic.  This particular variant has been reported in an individual affected with ovarian cancer (PMID: 22006311). This variant is also known as (c.5175delAA, p.Lys1649fsX15) in the literature. ClinVar contains an entry for this variant (Variation ID: 51747). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000131072 SCV000186002 pathogenic Hereditary cancer-predisposing syndrome 2018-07-31 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113361 SCV000327109 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000478026 SCV000567519 pathogenic not provided 2018-08-21 criteria provided, single submitter clinical testing This deletion of two nucleotides in BRCA2 is denoted c.4947_4948delAA at the cDNA level and p.Pro1651CysfsX14 (P1651CfsX14) at the protein level. The normal sequence, with the bases that are deleted in brackets, is CAAA[delAA]GTCC. The deletion causes a frameshift, which changes a Proline to a Cysteine at codon 1651, and creates a premature stop codon at position 14 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.4947_4948delAA, previously reported as 5175delAA using alternate nomenclature, has been observed in individuals with breast, ovarian, and/or pancreatic cancer (Walsh 2011, Zhen 2015). We consider this variant to be pathogenic.
Breast Cancer Information Core (BIC) (BRCA2) RCV000113361 SCV000146511 pathogenic Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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