Submissions for variant NM_007294.4(BRCA1):c.2704del (p.Glu902fs)

dbSNP: rs886040064

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000257123	SCV000323504	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-10-18	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	RCV000257123	SCV000325438	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Invitae	RCV001066878	SCV001231901	pathogenic	Hereditary breast ovarian cancer syndrome	2019-02-11	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 266295). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu902Asnfs*98) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics	RCV002429201	SCV002742155	pathogenic	Hereditary cancer-predisposing syndrome	2021-12-16	criteria provided, single submitter	clinical testing	The c.2704delG pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 2704, causing a translational frameshift with a predicted alternate stop codon (p.E902Nfs*98). This alteration was detected in cohort of 2733 patients with breast cancer diagnosed at 40 and younger (Copson ER et al. Lancet Oncol, 2018 02;19:169-180). This alteration was also reported in 1/60,466 breast cancer cases and in 1/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). 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.
Baylor Genetics	RCV000257123	SCV004216964	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2022-05-19	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003477874	SCV004219321	pathogenic	not provided	2022-11-04	criteria provided, single submitter	clinical testing	This frameshift variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in individuals with breast cancer as well as in unaffected controls in a breast cancer association study (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/BRCA1)). Based on the available information, this variant is classified as pathogenic.