Submissions for variant NM_007294.4(BRCA1):c.2351_2357del (p.Ser784fs)

dbSNP: rs80357820

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000111831	SCV000299749	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.
Department of Medical Genetics, Oslo University Hospital	RCV000111831	SCV000564335	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-07-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001176763	SCV001340811	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant deletes 7 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. 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496601	SCV001583463	pathogenic	Hereditary breast ovarian cancer syndrome	2024-01-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser784Trpfs*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 breast and/or ovarian cancer (PMID: 17574839, 29339979). This variant is also known as c.2470del7. ClinVar contains an entry for this variant (Variation ID: 54544). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001539163	SCV001756907	pathogenic	not provided	2023-12-05	criteria provided, single submitter	clinical testing	Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; 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 in large population cohorts (gnomAD); Also known as 2470_2476delCGTTACT; This variant is associated with the following publications: (PMID: 17574839, 29339979, 30678073, 32050665, 20104584, 35216584)
Ambry Genetics	RCV001176763	SCV002733608	pathogenic	Hereditary cancer-predisposing syndrome	2021-06-25	criteria provided, single submitter	clinical testing	The c.2351_2357delCGTTACT pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of 7 nucleotides at nucleotide positions 2351 to 2357, causing a translational frameshift with a predicted alternate stop codon (p.S784Wfs*6). This mutation has been reported in multiple Norwegian HBOC families (Møller P et al. Eur J Cancer, 2007 Jul;43:1713-7; Heramb C et al. Hered Cancer Clin Pract, 2018 Jan;16:3). Of note, this alteration is also designated as 2470del7 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.
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111831	SCV000144389	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	RCV000496601	SCV000587207	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research