Submissions for variant NM_000059.4(BRCA2):c.712G>T (p.Glu238Ter)

dbSNP: rs56383036

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000162051	SCV000300348	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-09-08	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	RCV000162051	SCV000327595	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Medical University Innsbruck	RCV000162051	SCV000212012	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-02-11	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355867	SCV001550876	pathogenic	Malignant tumor of breast		no assertion criteria provided	clinical testing	The BRCA2 p.Glu238* variant was not identified in the literature nor was it identified in the UMD-LSDB database. The variant was identified in dbSNP (ID: rs56383036) as "With Pathogenic, Uncertain significance allele", ClinVar (classified as pathogenic by three submitters), and in LOVD 3.0 (4X as pathogenic).The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.712G>T variant leads to a premature stop codon at position 238 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the BRCA2 gene are an established mechanism of disease in BRCA2 associated cancers and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic.