Submissions for variant NM_007294.4(BRCA1):c.3253dup (p.Arg1085fs)

dbSNP: rs80357517

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000077125	SCV000299899	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	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	RCV000077125	SCV000325585	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000483228	SCV000566135	pathogenic	not provided	2020-06-23	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Casadei 2001, Azzolini 2016); Not observed in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as c.3372dupA; This variant is associated with the following publications: (PMID: 10660329, 27062684, 11556835)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496900	SCV002172981	pathogenic	Hereditary breast ovarian cancer syndrome	2021-10-25	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 54805). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 27062684). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg1085Lysfs*8) 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).
Ambry Genetics	RCV004609302	SCV005100944	pathogenic	Hereditary cancer-predisposing syndrome	2024-03-20	criteria provided, single submitter	clinical testing	The c.3253dupA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a duplication of A at nucleotide position 3253, causing a translational frameshift with a predicted alternate stop codon (p.R1085Kfs*8). This alteration has been reported in multiple individuals with personal and/or family history consistent with breast and/or ovarian carcinoma (HBOC) syndrome (De Benedetti VM et al. Hum. Mutat.,1998;12:215; Azzollini J et al. Eur. J. Intern. Med., 2016 Jul;32:65-71; Rebbeck TR et al. Hum. Mutat., 2018 May;39:593-620). 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. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). As such, this alteration is interpreted as a disease-causing mutation.
Sharing Clinical Reports Project (SCRP)	RCV000077125	SCV000108922	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2011-08-16	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000077125	SCV000144685	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2002-05-29	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496900	SCV000587288	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research