Submissions for variant NM_000059.4(BRCA2):c.1909+2T>A

dbSNP: rs876658577

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000214167	SCV000274010	likely pathogenic	Hereditary cancer-predisposing syndrome	2015-02-24	criteria provided, single submitter	clinical testing	The c.1909+2T>A intronic variant (also known as IVS10+2T>A) results from a T to A substitution two nucleotides after coding exon 9 in the BRCA2 gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6249 samples (12498 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 105000 alleles tested) in our clinical cohort. This nucleotide position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native donor splice site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice donor site are typically deleterious in nature (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). As such, the c.1909+2T>A variant is classified as likely pathogenic.
Medical Genetics UMG, Mater Domini University Hospital/ Magna Graecia University of Catanzaro	RCV002279716	SCV002567962	likely pathogenic	Familial cancer of breast		criteria provided, single submitter	clinical testing