Submissions for variant NM_007294.4(BRCA1):c.2515del (p.His839fs)

dbSNP: rs80357607

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000031055	SCV000299782	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.
Ambry Genetics	RCV000131999	SCV000187058	pathogenic	Hereditary cancer-predisposing syndrome	2021-10-25	criteria provided, single submitter	clinical testing	The c.2515delC pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 2515, causing a translational frameshift with a predicted alternate stop codon (p.H839Tfs*7). This mutation has been identified in multiple patients with a history of breast and/or ovarian cancer (King MC et al. JAMA. 2001 Nov 14;286(18):2251-6; Borg A et al. Hum Mutat. 2010 Mar;31(3):E1200-40; Zhang S et al. Gynecol. Oncol. 2011 May;121:353-7; Yadav S et al. J Clin Oncol, 2020 05;38:1409-1418) and also in a female patient who was diagnosed with Wilms' tumor at age 6 and breast cancer at age 21 (Dulude AM et al. Clin Breast Cancer. 2011 Aug;11(4):268-9). Of note, this alteration is also designated 2634delC in published literature. 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.
GeneDx	RCV000236698	SCV000292994	pathogenic	not provided	2022-05-16	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; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 2634delC; This variant is associated with the following publications: (PMID: 11710890, 21324516, 20104584, 21729660, 16267036, 28152038)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000031055	SCV000325380	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000131999	SCV000905033	pathogenic	Hereditary cancer-predisposing syndrome	2021-06-03	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide 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. This variant has been reported in individuals affected with breast cancer (PMID: 20104584, 28715532). 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.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000236698	SCV001446537	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Invitae	RCV000496628	SCV001583461	pathogenic	Hereditary breast ovarian cancer syndrome	2023-05-12	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: 37474). This variant is also known as 2634delC, Stop 845. This premature translational stop signal has been observed in individual(s) with Wilms' tumor and breast cancer (PMID: 11710890, 20104584, 21729660). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His839Thrfs*7) 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).
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000236698	SCV002009458	pathogenic	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000236698	SCV003812387	pathogenic	not provided	2022-11-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000031055	SCV004215143	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2023-05-03	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000031055	SCV000053649	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2010-10-15	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000031055	SCV000144464	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	RCV000496628	SCV000587227	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne	RCV000785404	SCV000923976	pathogenic	Neoplasm of ovary	2018-12-01	no assertion criteria provided	research