ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.631G>C (p.Val211Leu) (rs80358871)

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Total submissions: 6
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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 RCV000031617 SCV000327390 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
GeneDx RCV000438397 SCV000515973 pathogenic not provided 2015-03-18 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.631G>C at the cDNA level. Using alternate nomenclature, This variant would be defined as BRCA2 859G>C. Although the nucleotide substitution results in the change of a Valine to a Leucine at codon 211, and is called Val211Leu in the literature, we are using only the nucleotide nomenclature to refer to the mutation since the defect is determined to be one of splicing rather than a resulting missense pathogenic variant. Multiple splicing models predict that this variant may destroy the natural splice donor site for intron 7 and lead to abnormal splicing. Consistent with the splicing models, an in vitro minigene assay found that a significant proportion of transcripts produced from BRCA2 c.631G>C were missing exon 7 (Di Giacomo 2013). BRCA2 c.631G>C was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The nucleotide which is altered, a guanine (G) at base 631, is conserved across species. Based on the current evidence, we consider this variant to be pathogenic.
Ambry Genetics RCV000562565 SCV000665043 likely pathogenic Hereditary cancer-predisposing syndrome 2019-09-16 criteria provided, single submitter clinical testing Last nucleotide of exon;Functionally-validated splicing mutation;Rarity in general population databases (dbsnp, esp, 1000 genomes)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000438397 SCV000887871 pathogenic not provided 2017-11-20 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031617 SCV000054224 pathogenic Breast-ovarian cancer, familial 2 2013-10-09 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031617 SCV000147342 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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