ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6393_6396del (p.Lys2131fs) (rs397507849)

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Total submissions: 4
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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) RCV000211011 SCV000301031 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 RCV000166186 SCV000216962 pathogenic Hereditary cancer-predisposing syndrome 2018-01-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Michigan Medical Genetics Laboratories,University of Michigan RCV000211011 SCV000267795 pathogenic Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
GeneDx RCV000478975 SCV000568475 pathogenic not provided 2017-06-29 criteria provided, single submitter clinical testing This deletion of four nucleotides in BRCA2 is denoted c.6393_6396delATTA at the cDNA level and p.Lys2131AsnfsX5 (K2131NfsX5) at the protein level. Using alternate nomenclature, this variant has been published as BRCA2 6621del4. The normal sequence, with the bases that are deleted in brackets, is TTAA[delATTA]TCAA. The deletion causes a frameshift which changes a Lysine to an Asparagine at codon 2131, and creates a premature stop codon at position 5 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.6393_6396delATTA has been observed in at least two individuals with ovarian cancer as well as in a male with breast cancer whose tumor showed loss of the wild-type BRCA2 allele (Kwiatkowska 2002, Brozek 2008, Koczkowska 2016). We consider this variant to be pathogenic.

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