ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1379del (p.Asn460fs) (rs1064793945)

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Total submissions: 3
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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) RCV000661496 SCV000783781 pathogenic Breast-ovarian cancer, familial 2 2017-12-15 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000479208 SCV000567425 pathogenic not provided 2015-07-21 criteria provided, single submitter clinical testing This deletion of one nucleotide in BRCA2 is denoted c.1379delA at the cDNA level and p.Asn460MetfsX6 (N460MfsX6) at the protein level. The normal sequence, with the base that is deleted in braces, is TTAA[A]TGAG. The deletion causes a frameshift, which changes an Asparagine to a Methionine at codon 460, and creates a premature stop codon at position 6 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. we consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000590677 SCV000694535 likely pathogenic Hereditary breast and ovarian cancer syndrome 2016-01-08 criteria provided, single submitter clinical testing Variant summary: The c.1379delA variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein, which is a commonly known mechanism for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g.c.1496_1497delAG, c.1767_1770delGTTT). One in-silico tool predicts damaging outcome for this variant. This variant is not found in 120672 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant was classified as likely pathogenic.

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