Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002407415 | SCV002716721 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-02-23 | criteria provided, single submitter | clinical testing | The c.173_211+2147del2186 pathogenic mutation includes at least a portion of coding exon 1 through at least a portion of intron 1 in the MSH2 gene. This variant has been identified in a proband whose Lynch syndrome-associated tumor demonstrated loss of both MSH2/MSH6 expression by immunohistochemistry (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In silico splice site analysis predicts that this alteration will weaken the native splice donor site and result in the creation or strengthening of a novel splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation. |