Submissions for variant NM_007294.4(BRCA1):c.3084_3094del (p.Asn1029fs)

dbSNP: rs80357647

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000077537	SCV000299880	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000048068	SCV000076081	pathogenic	Hereditary breast ovarian cancer syndrome	2023-05-19	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 54768). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer and triple-negative breast cancer (PMID: 17574839, 23199084, 25452441). It is commonly reported in individuals of Norwegian ancestry (PMID: 17574839, 23199084, 25452441). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn1029Argfs*5) 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). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000213895	SCV000275779	pathogenic	Hereditary cancer-predisposing syndrome	2015-05-15	criteria provided, single submitter	clinical testing	The c.3084_3094delTAATAACATTA pathogenic mutation (also known as3203del11), located in coding exon 9 of the BRCA1 gene, results from a deletion of 11 nucleotides between nucleotide positions 3084 and 3094, causing a translational frameshift with a predicted alternate stop codon. Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
GeneDx	RCV000255873	SCV000322082	pathogenic	not provided	2023-11-07	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 3203_3213del11; This variant is associated with the following publications: (PMID: 16267036, 23199084, 24312913, 17574839, 11334729, 11720839, 12481264, 25452441, 29339979, 35216584, 34981296)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000077537	SCV000325552	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Department of Medical Genetics, Oslo University Hospital	RCV000077537	SCV000564355	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-01-12	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000255873	SCV000600316	pathogenic	not provided	2016-09-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000048068	SCV000699003	pathogenic	Hereditary breast ovarian cancer syndrome	2021-12-02	criteria provided, single submitter	clinical testing	Variant summary: BRCA1 c.3084_3094del11 (p.Asn1029ArgfsX5) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251142 control chromosomes and c.3084_3094del11 has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example: Moller_2001, Judkins_2005, Couch_2015, Grindedal_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven ClinVar submitters have assessed this variant after 2014, including one expert panel and one consortium: all submitters have classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Revvity Omics, Revvity	RCV000255873	SCV003817993	pathogenic	not provided	2022-02-10	criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000255873	SCV005198095	pathogenic	not provided	2023-08-18	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000077537	SCV000109338	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2012-08-18	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000077537	SCV000144631	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	1999-08-31	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000048068	SCV000587279	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
BRCAlab, Lund University	RCV000077537	SCV002589104	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2022-08-26	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004758625	SCV005359986	pathogenic	BRCA1-related disorder	2024-03-12	no assertion criteria provided	clinical testing	The BRCA1 c.3084_3094del11 variant is predicted to result in a frameshift and premature protein termination (p.Asn1029Argfs*5). In the literature this variant is also referred to as c.3203del11 or c.3084del11. This variant has been reported in individuals with breast and ovarian cancer (Moller et al. 2001. PubMed: 11334729; Moller et al. 2007. PubMed ID: 17574839; Heramb et al. 2018. PubMed ID: 29339979; Janavicius et al. 2010. PubMed ID: 23199084). Of note, this variant has commonly been reported in individuals of Norwegian descent (Moller et al. 2001. PubMed: 11334729; Janavicius et al. 2010. PubMed ID: 23199084; Heramb et al. 2018. PubMed ID: 29339979). This variant has not been reported in a large population database, indicating this variant is rare, and has been reported as pathogenic by multiple laboratories in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/54768/). Frameshift variants in BRCA1 are expected to be pathogenic. This variant is interpreted as pathogenic.