Submissions for variant NM_007294.4(BRCA1):c.5249dup (p.Arg1751fs)

dbSNP: rs879253993

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000661198	SCV000783454	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2017-12-15	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics	RCV003163047	SCV003856650	pathogenic	Hereditary cancer-predisposing syndrome	2023-01-30	criteria provided, single submitter	clinical testing	The c.5249dupA pathogenic mutation, located in coding exon 18 of the BRCA1 gene, results from a duplication of A at nucleotide position 5249, causing a translational frameshift with a predicted alternate stop codon (p.R1751Afs*79). This alteration occurs at the 3' terminus of theBRCA1 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 114 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496398	SCV000587481	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research