Submissions for variant NM_000059.4(BRCA2):c.5254del (p.His1752fs)

dbSNP: rs397507777

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000257776	SCV000324327	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-10-18	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics	RCV000214583	SCV000275041	pathogenic	Hereditary cancer-predisposing syndrome	2020-04-27	criteria provided, single submitter	clinical testing	The c.5254delC pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 5254, causing a translational frameshift with a predicted alternate stop codon (p.H1752Ifs*25). Also designated as 5482delC in published literature, this alteration was seen in a male patient diagnosed with breast cancer at age 70 (Tai YC et al. J. Natl. Cancer Inst. 2007 Dec;99(23):1811-4). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000257776	SCV000327187	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001008101	SCV001167848	pathogenic	not provided	2018-05-22	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in BRCA2 is denoted c.5254delC at the cDNA level and p.His1752IlefsX25 (H1752IfsX25) at the protein level. The normal sequence, with the base that is deleted in brackets, is CTAC[delC]ATTC. The deletion causes a frameshift, which changes a Histidine to an Isoleucine at codon 1752 and creates a premature stop codon at position 25 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.5254delC, also reported as 5482delC using alternate nomenclature, has been observed in an individual with male breast cancer who had a family history of breast cancer (Tai 2007). We consider this variant to be pathogenic.
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496225	SCV000587755	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research