ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4263dup (p.Glu1422Ter) (rs1555283664)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000564227 SCV000666025 pathogenic Hereditary cancer-predisposing syndrome 2017-12-24 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)
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000661568 SCV000783862 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 RCV000482646 SCV000566730 pathogenic not provided 2015-05-26 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.4263dupT at the cDNA level and p.Glu1422Ter (E1422X) at the protein level. The duplication creates a nonsense variant, which changes a Glutamic Acid to a premature stop codon (GAG>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000588972 SCV000694757 likely pathogenic Hereditary breast and ovarian cancer syndrome 2016-02-23 criteria provided, single submitter clinical testing Variant summary: The c.4263dupT 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.4712_4713delAG). One in-silico tool predicts damaging outcome for this variant. This variant is not found in 119534 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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