Submissions for variant NM_007294.4(BRCA1):c.2486_2487del (p.Gly828_Phe829insTer)

dbSNP: rs80357658

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)	RCV000661101	SCV000783348	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	RCV001015715	SCV001176579	pathogenic	Hereditary cancer-predisposing syndrome	2021-09-01	criteria provided, single submitter	clinical testing	The c.2486_2487delTT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 2486 to 2487, causing a translational frameshift with a predicted alternate stop codon (p.F829*). This alteration has been reported in multiple Chilean breast and/or ovarian cancer families (Jara L et al. Cancer Genet. Cytogenet., 2006 Apr;166:36-45; Gonzalez-Hormazabal P et al. Breast Cancer Res. Treat., 2011 Apr;126:705-16; Alvarez C et al. Oncotarget, 2017 Sep;8:74233-74243; Cardoso FC et al. Hum Genomics, 2018 08;12:39). 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.
Invitae	RCV001053717	SCV001217993	pathogenic	Hereditary breast ovarian cancer syndrome	2023-12-17	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe829*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with epithelial ovarian cancer (PMID: 30103829). ClinVar contains an entry for this variant (Variation ID: 54583). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV001015715	SCV001340807	pathogenic	Hereditary cancer-predisposing syndrome	2021-04-20	criteria provided, single submitter	clinical testing	This variant deletes 2 nucleotides in exon 10 of the BRCA1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least four individuals affected with breast and ovarian cancer (PMID: 16616110, 20859677, 30103829; Color internal data). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000577749	SCV000679531	not provided	Familial cancer of breast		no assertion provided	literature only