Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193889 | SCV001363048 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2019-07-05 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.517-2A>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant shifts a 3' acceptor site to 9 nucleotides downstream, which would create an in-frame shift. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251306 control chromosomes. c.517-2A>T has been reported in the literature in an individual affected with Hereditary Breast and Ovarian Cancer (Sunami_2019). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |