Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV001829305 | SCV002097107 | uncertain significance | Hermansky-Pudlak syndrome | 2021-11-29 | criteria provided, single submitter | curation | The p.Gly596Val variant in HPS1 has been reported in 1 individual, in the compound heterozygous state, with Hermansky-Pudlak syndrome (PMID: 31141302) and has been identified in 0.006% (1/16198) of African/African-American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs139951191). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_supporting, PM3, PP3 (Richards 2015). |