Submissions for variant NM_007294.4(BRCA1):c.1713_1717del (p.Glu572fs)

dbSNP: rs80357640

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000077494	SCV000299638	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	RCV000077494	SCV000325124	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000483355	SCV000568425	pathogenic	not provided	2024-02-27	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; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 1832del5, 1832_1836delAGAAT; This variant is associated with the following publications: (PMID: 11030417, 12716036, 15322516, 9150171, 9667259, 16234499, 17591843, 10630184, 23958087, 10800284, 12491487, 15863708, 12048272, 25428789, 18159056, 30322717)
Ambry Genetics	RCV000571930	SCV000660940	pathogenic	Hereditary cancer-predisposing syndrome	2022-03-14	criteria provided, single submitter	clinical testing	The c.1713_1717delAGAAT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of 5 nucleotides at nucleotide positions 1713 to 1717, causing a translational frameshift with a predicted alternate stop codon (p.E572Tfs*12). This mutation has been reported in multiple individuals and families with breast and/or ovarian cancer (Euhus DM et al. J. Natl. Cancer Inst., 2002 Jun;94:844-51; Frank TS et al. J. Clin. Oncol., 1998 Jul;16:2417-25; Gao Q et al. Am. J. Hum. Genet., 1997 May;60:1233-6). This mutation has also been reported as a potential founder mutation in African Americans based on haplotype analysis (Gao Q et al. Am. J. Hum. Genet., 1997 May;60:1233-6; Olopade OI et al. Cancer, 2003 Jan;97:236-45). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000483355	SCV001133494	pathogenic	not provided	2024-11-25	criteria provided, single submitter	clinical testing	The BRCA1 c.1713_1717del (p.Glu572Thrfs*12) variant alters the translational reading frame of the BRCA1 mRNA and causes the premature termination of BRCA1 protein synthesis. This variant has been described in the published literature in as a founder variant in the African American population and has been detected in individuals with a personal and/or family history of breast and/or ovarian cancer (PMIDs: 9150171 (1997), 9667259 (1998), 16234499 (2005), 18159056 (2007) and 25428789 (2015), 32025337 (2020), and 35216584 (2022)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496485	SCV001585369	pathogenic	Hereditary breast ovarian cancer syndrome	2024-04-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu572Thrfs*12) 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 breast cancer and ovarian cancer (PMID: 9150171, 9667259, 12048272, 12491487, 16234499). It has also been observed to segregate with disease in related individuals. This variant is also known as 1832del5. ClinVar contains an entry for this variant (Variation ID: 54331). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV000077494	SCV004216882	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2022-11-22	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000077494	SCV000109292	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2006-03-09	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000077494	SCV000144163	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	1997-11-14	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496485	SCV000587158	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research