Submissions for variant NM_007294.4(BRCA1):c.5193+1G>C

dbSNP: rs80358004

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000131171	SCV000186117	pathogenic	Hereditary cancer-predisposing syndrome	2013-01-08	criteria provided, single submitter	clinical testing	In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000112550	SCV000326199	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
GeneDx	RCV000486220	SCV000568397	pathogenic	not provided	2021-03-11	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate a damaging effect: variant classified as non-functional based on a saturation genome editing (SGE) assay measuring cell survival (Findlay 2018); Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Kwong 2012, Ryu 2019); Not observed in large population cohorts (Lek 2016); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 5312+1G>C; This variant is associated with the following publications: (PMID: 22970155, 23239986, 30209399, 30702160, 30350268, 29446198, 31825140)
Labcorp Genetics (formerly Invitae), Labcorp	RCV003529968	SCV004297793	pathogenic	Hereditary breast ovarian cancer syndrome	2024-03-15	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 18 of the BRCA1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with breast and/or ovarian cancer (PMID: 22970155, 30350268, 30702160, 31825140, 34645131). ClinVar contains an entry for this variant (Variation ID: 55448). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that disruption of this splice site affects BRCA1 function (PMID: 30209399). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV005357413	SCV005915327	pathogenic	Fanconi anemia, complementation group S	2020-05-28	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000112550	SCV000145379	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2013-02-20	no assertion criteria provided	clinical testing
Brotman Baty Institute, University of Washington	RCV000112550	SCV001242334	not provided	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion provided	in vitro