In STRchive v2.17.1, the hg38 Stranger catalog entry for SBMA_AR uses ReferenceRegion chrX:67545316-67545419 with LocusStructure=(GCA)*, NormalMax=34, PathologicMin=38. Running ExpansionHunter 5.0.0 + Stranger 0.10.0 on the GIAB NA12878/HG001 30x BAM with the STRchive v2.17.1 catalog produced SBMA_AR allele sizes 34/38 and Stranger classified it as full_mutation/pathogenic.
This is discordant with the expected NA12878 AR CAG sizing (~20-25; our prior seed-catalog run over chrX:67545316-67545385 reported 21/25) and suggests the longer region may be including flanking sequence or otherwise measuring a different tract than the canonical AR CAG repeat used for SBMA interpretation.
Catalog entry observed locally:
{
"LocusId": "SBMA_AR",
"ReferenceRegion": "chrX:67545316-67545419",
"LocusStructure": "(GCA)*",
"DisplayRU": "GCA",
"NormalMax": 34,
"PathologicMin": 38,
"Gene": "AR",
"Disease": "SBMA"
}For safety in our downstream clinical-adjacent pipeline, we are marking SBMA_AR not-callable pending upstream validation rather than surfacing the NA12878 pathogenic call. Could you confirm whether this hg38 region is intended to include only the canonical AR CAG/GCA tract for SBMA?
In STRchive v2.17.1, the hg38 Stranger catalog entry for SBMA_AR uses ReferenceRegion
chrX:67545316-67545419withLocusStructure=(GCA)*,NormalMax=34,PathologicMin=38. Running ExpansionHunter 5.0.0 + Stranger 0.10.0 on the GIAB NA12878/HG001 30x BAM with the STRchive v2.17.1 catalog produced SBMA_AR allele sizes34/38and Stranger classified it as full_mutation/pathogenic.This is discordant with the expected NA12878 AR CAG sizing (~20-25; our prior seed-catalog run over
chrX:67545316-67545385reported21/25) and suggests the longer region may be including flanking sequence or otherwise measuring a different tract than the canonical AR CAG repeat used for SBMA interpretation.Catalog entry observed locally:
{ "LocusId": "SBMA_AR", "ReferenceRegion": "chrX:67545316-67545419", "LocusStructure": "(GCA)*", "DisplayRU": "GCA", "NormalMax": 34, "PathologicMin": 38, "Gene": "AR", "Disease": "SBMA" }For safety in our downstream clinical-adjacent pipeline, we are marking SBMA_AR not-callable pending upstream validation rather than surfacing the NA12878 pathogenic call. Could you confirm whether this hg38 region is intended to include only the canonical AR CAG/GCA tract for SBMA?