ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8915del (p.Leu2972fs) (rs397508019)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000257384 SCV000327988 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000257384 SCV000324707 pathogenic Breast-ovarian cancer, familial 2 2016-10-18 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000657233 SCV000778959 pathogenic not provided 2018-02-08 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.8915delT at the cDNA level and p.Leu2972CysfsX4 (L2972CfsX4) at the protein level. The normal sequence, with the base that is deleted in brackets, is AAGT[delT]GCGT. The deletion causes a frameshift which changes a Leucine to a Cysteine at codon 2972, and creates a premature stop codon at position 4 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.8915delT, also defined as BRCA2 8914delT and BRCA2 9143delT using alternate nomenclature, has been observed in multiple individuals with breast cancer (Ang 2007, Kim 2012, Wong 2015). We consider this variant to be pathogenic.
Invitae RCV000045655 SCV000073668 pathogenic Hereditary breast and ovarian cancer syndrome 2016-04-23 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 22 of the BRCA2 mRNA (c.8915delT), causing a frameshift at codon 2972. This creates a premature translational stop signal (p.Leu2972Cysfs*4) and is expected to result in an absent or disrupted protein product. Truncating variants in BRCA2 are known to be pathogenic. This particular truncation has been reported in patients affected with breast cancer (PMID: 18006916, 22798144, 26221963). This variant is also known as 9143delT in the literature. For these reasons, this variant has been classified as Pathogenic.

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