Submissions for variant NM_032043.2(BRIP1):c.2905+4T>C (rs373835270)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000565993	SCV000666183	uncertain significance	Hereditary cancer-predisposing syndrome	2016-10-13	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: Insufficient evidence
Invitae	RCV000636100	SCV000757532	uncertain significance	Familial cancer of breast; Fanconi anemia, complementation group J	2017-12-15	criteria provided, single submitter	clinical testing	This sequence change falls in intron 19 of the BRIP1 gene. It does not directly change the encoded amino acid sequence of the BRIP1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs373835270, ExAC 0.002%). This variant has not been reported in the literature in individuals with BRIP1-related disease. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.