Submissions for variant NM_007294.4(BRCA1):c.2131_2132del (p.Lys711fs)

dbSNP: rs398122653

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000077094	SCV000299703	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	RCV000164437	SCV000215077	pathogenic	Hereditary cancer-predisposing syndrome	2016-07-18	criteria provided, single submitter	clinical testing	The c.2131_2132delAA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of two nucleotides at nucleotide positions 2131 to 2132, causing a translational frameshift with a predicted alternate stop codon (p.K711Vfs*6). This alteration has been identified on hereditary cancer predisposition multigene panel testing in an ovarian cancer patient (Lilyquist J et al. Gynecol. Oncol., 2017 11;147:375-380). 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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000077094	SCV000325253	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Invitae	RCV000474010	SCV000549300	pathogenic	Hereditary breast ovarian cancer syndrome	2023-08-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys711Valfs*6) 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 high risk of breast and/or ovarian cancer (PMID: 29446198). ClinVar contains an entry for this variant (Variation ID: 91577). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000164437	SCV000905205	pathogenic	Hereditary cancer-predisposing syndrome	2020-12-29	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 observed in one individual each affected with ovarian cancer (PMID: 28888541) and breast cancer (PMID: 31706072) and a suspected hereditary breast and ovarian cancer family (PMID: 29446198). 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.
GeneDx	RCV003325458	SCV004031933	pathogenic	not provided	2023-03-02	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; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Lilyquist et al., 2017; Rebbeck et al., 2018; Akcay et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); Also known as 2250_2252del; This variant is associated with the following publications: (PMID: 31706072, 28888541, 28152038, 29446198, 31853058, 32658311)
Sharing Clinical Reports Project (SCRP)	RCV000077094	SCV000108891	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2009-06-09	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000474010	SCV000587188	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences	RCV001554333	SCV001775546	pathogenic	Breast carcinoma	2021-08-10	no assertion criteria provided	clinical testing	Pathology: Invasive breast Carcinoma ER: 0 , PR: 0 , HER2: 0, KI67: -