Submissions for variant NM_007294.4(BRCA1):c.5106del (p.Lys1702fs)

dbSNP: rs80357553

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)	RCV000112499	SCV000300201	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	RCV000048796	SCV000076809	pathogenic	Hereditary breast ovarian cancer syndrome	2022-09-01	criteria provided, single submitter	clinical testing	This premature translational stop signal has been observed in individual(s) with breast/ovarian cancer (PMID: 11938448, 17148771). This variant is also known as 5225delA. ClinVar contains an entry for this variant (Variation ID: 55402). For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys1702Asnfs*4) 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	RCV000166104	SCV000216871	pathogenic	Hereditary cancer-predisposing syndrome	2014-09-22	criteria provided, single submitter	clinical testing	The c.5106delA pathogenic mutation (also known as 5225delA), located in coding exon 16 of the BRCA1 gene, results from a deletion of one nucleotide at nucleotide position 5106, causing a translational frameshift with a predicted alternate stop codon. This mutation has been identified in an Italian breast/ovarian cancer family (Nedelcu R, Eur. J. Hum. Genet. 2002 Feb; 10(2):150-2). In addition to the clinical data presented in the literature, 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).
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000112499	SCV000326156	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001353569	SCV003761566	pathogenic	not provided	2022-07-26	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 5225del; This variant is associated with the following publications: (PMID: 11938448, 32341426, 17148771, 32438681, 31853058)
All of Us Research Program, National Institutes of Health	RCV004804016	SCV004817590	pathogenic	BRCA1-related cancer predisposition	2024-06-27	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 17 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 an individual affected with ovarian cancer and two families affected with breast and/or ovarian cancer (PMID: 11938448, 17148771, 32438681). 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.
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112499	SCV000145315	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	RCV000048796	SCV000587464	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353569	SCV000591580	pathogenic	not provided		no assertion criteria provided	clinical testing	NVA pending - needed. This is the type of variant expected to cause the disorder. See case BB5454 for familial report
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research	RCV000735493	SCV000863631	pathogenic	Breast and/or ovarian cancer	2015-09-16	no assertion criteria provided	clinical testing