ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8174G>A (p.Trp2725Ter) (rs730881581)

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Total submissions: 5
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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 RCV000241299 SCV000327829 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) RCV000241299 SCV000301248 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000160191 SCV000210536 pathogenic not provided 2016-11-14 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.8174G>A at the cDNA level and p.Trp2725Ter (W2725X) at the protein level. Using alternate nomenclature, this variant would be defined as BRCA2 8402G>A. The substitution creates a nonsense variant, which changes a Tryptophan to a premature stop codon (TGG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in at least one individual with breast cancer (Susswein 2015) and is considered pathogenic.
Invitae RCV000460183 SCV000549820 pathogenic Hereditary breast and ovarian cancer syndrome 2016-10-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 2725 (p.Trp2725*) of the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic. This particular variant has been reported in the literature in an individual affected with breast cancer (PMID: 26681312) as well as two individuals with family histories of breast cancer (PMID: 22366370). A different variant (c.8175G>A) giving rise to the same protein effect (p.Trp2725*) has been reported in 2 families affected with breast cancer (PMID: 22923021). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000460183 SCV000838868 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing

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