Submissions for variant NM_007294.4(BRCA1):c.2727_2730del (p.Asn909fs)

dbSNP: rs80357605

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)	RCV000083188	SCV000299824	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	RCV000047948	SCV000075961	pathogenic	Hereditary breast ovarian cancer syndrome	2023-07-16	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asn909Lysfs*90) 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 cancer and/or ovarian cancer (PMID: 8968102, 16683254, 22762150). This variant is also known as 2846delTCAA. ClinVar contains an entry for this variant (Variation ID: 54661). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000162859	SCV000213346	pathogenic	Hereditary cancer-predisposing syndrome	2018-02-23	criteria provided, single submitter	clinical testing	The c.2727_2730delTCAA pathogenic mutation, located in coding exon 9 of the BRCA1 gene, results from a deletion of 4 nucleotides at nucleotide positions 2727 to 2730, causing a translational frameshift with a predicted alternate stop codon (p.N909Kfs*90). This mutation has previously been reported in an Italian family affected with breast/ovarian cancer (Montagna M et al. Cancer Res. 1996 Dec;56(23):5466-9). Of note, this alteration is also designated as 2846del4 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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000083188	SCV000325450	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Department of Medical Genetics, Oslo University Hospital	RCV000083188	SCV000564301	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-07-01	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000083188	SCV000115262	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2012-05-01	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000083188	SCV000144528	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	1999-06-22	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000047948	SCV000587252	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research