Submissions for variant NM_007294.4(BRCA1):c.5467+5G>C

dbSNP: rs397509287

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV004018962	SCV005026102	likely pathogenic	Hereditary cancer-predisposing syndrome	2024-02-01	criteria provided, single submitter	clinical testing	The c.5467+5G>C intronic variant results from a G to C substitution 5 nucleotides after coding exon 21 in the BRCA1 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing (Whiley PJ et al. Hum Mutat, 2011 Jun;32:678-87; Whiley PJ et al. Clin Chem. 2014 Feb;60(2):341-52). One functional study found that this nucleotide substitution is non-functional in a high throughput genome editing haploid cell survival assay (Findlay GM et al. Nature, 2018 Oct;562:217-222). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000577140	SCV000679304	not provided	Familial cancer of breast		no assertion provided	literature only
Brotman Baty Institute, University of Washington	RCV001076242	SCV001241960	not provided	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion provided	in vitro