Franklin's SMA biomarker reports copy number (CN) information for SMN1 and SM2 genes and the silent carrier predictor variant c.*3+80T>G in the SMN1 gene.
Scope
The SMA biomarker can be included in germline cases. It requires an assay configuration.
The SMA biomarker is not available for somatic cases.
The SMA biomarker typically displays CN information based on Dragen targeted caller output. Feature requests for biomarker display based on your custom input file should be addressed to Franklin support team ([email protected])
Biomarker Statuses
When configured in the assay, the SMA biomarker is displayed in the Additional Information section of the Workbench, showing one of the statuses as detailed in the table below. The table is sorted based on status precedence, in descending order.
Franklin status | Condition | Displayed status | Displayed details | Tile stripe color |
Not tested | SMN1 copy number null / missing | SMA: Not tested | None | N/A (no tile) |
Call failed | Dragen ponQualityFilter present and ≠ "PASS" (relevant for DRAGEN 4.4) | SMA: Call failed | Low PON correlation / Invalid PON correlation | N/A (no tile) |
Affected | SMN1 CN = 0 | Affected | SMN1 copy number: 0 | Red (similar to Pathogenic variant) |
Carrier | SMN1 CN = 1 | Carrier | SMN1 copy number: 1 | Grey (similar to VUS variant) |
Possible silent carrier (2+0) | SMN1 CN = 2 and predictor variant is present (c.*3+80T>G, alt CN > 0) | Silent carrier | 2+0 | Grey (similar to VUS variant) |
Negative | Any other case (CN = 2 without predictor variant, or CN > 2) | SMA: SMN1 <SMN2 CN> copies, SMN2 <SMN2 CN> copies | None | N/A (no tile) |
Limitations
The limitations below are inherent to CN based screening rather than specific to Franklin. As such, they apply to Franklin’s SMA biomarker:
CN information cannot determine whether two SMN1 copies are located in cis or trans.
The SMN1 c.*3+80T>G predictor variant may raise or lower clinical suspicion; it does not resolve the gene configuration.
A residual carrier risk remains after a Negative result, and may vary by ancestry.
Pathogenic sequence variants within SMN1 are not detected by CN analysis. Hence, an individual with CN=1 and a pathogenic variant on the other copy may be reported as a Carrier.
For these reasons the biomarker status is a screening signal for review. The user / laboratory are responsible for confirmatory testing and the final clinical interpretation.