Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001025743 | SCV001187993 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-02 | criteria provided, single submitter | clinical testing | The c.6866delT variant, located in coding exon 11 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 6866, causing a translational frameshift with a predicted alternate stop codon (p.L2289Yfs*2) in the reported isoform. However, coding exon 11 (also known as Exon 12 in the literature) is absent in a natural, in-frame isoform and this exon is also redundant based on clinical and functional studies (Fackenthal J et al. J Med Genet. 2016 Aug; 53(8):548-58; Li L et al. Hum Mutat. 2009 Nov; 30(11):1543-50). Alterations that result in premature protein truncation are typically deleterious in nature; however the occurrence of such alterations in exons that are absent in functional, alternate isoforms leads to the possibility that the alternate isoform can rescue the defect. As such, the clinical significance of this alteration remains unclear. |