ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.2959A>T (p.Lys987Ter) (rs878854941)

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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) RCV000256551 SCV000323543 pathogenic Breast-ovarian cancer, familial 1 2016-10-18 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000256551 SCV000325507 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000481554 SCV000569853 pathogenic not provided 2016-04-05 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.2959A>T at the cDNA level and p.Lys987Ter (K987X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA1 3078A>T. The substitution creates a nonsense variant, which changes a Lysine to a premature stop codon (AAG>TAG), 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 RCV000780985 SCV000918711 likely pathogenic Hereditary breast and ovarian cancer syndrome 2017-11-13 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2959A>T (p.Lys987X) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Leu1086X, p.Gln1111X, p.Glu1134X, etc.). This variant is absent in 245952 control chromosomes (gnomAD). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant is classified as likely pathogenic.

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