Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000585907 | SCV000695225 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2017-05-01 | criteria provided, single submitter | clinical testing | Variant summary: The BRCA2 c.9254delC (p.Thr3085Lysfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.9294C>G (p.Tyr3098X), c.9331G>T (p.Glu3111X), and c.9382C>T (p.Arg3128X)). This variant is absent in 119814 control chromosomes (ExAC). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic. |
| Ambry Genetics | RCV003352931 | SCV004052641 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-09-06 | criteria provided, single submitter | clinical testing | The c.9254delC pathogenic mutation, located in coding exon 23 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 9254, causing a translational frameshift with a predicted alternate stop codon (p.T3085Kfs*19). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |