Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetic Services Laboratory, |
RCV000500361 | SCV000595167 | pathogenic | Hermansky-Pudlak syndrome 1 | 2017-03-17 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001214000 | SCV001385663 | pathogenic | not provided | 2023-10-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asn78Metfs*43) in the HPS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HPS1 are known to be pathogenic (PMID: 12442288, 16185271). This variant is present in population databases (rs773323079, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with HPS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 435451). For these reasons, this variant has been classified as Pathogenic. |
| Broad Center for Mendelian Genomics, |
RCV001829427 | SCV002097073 | likely pathogenic | Hermansky-Pudlak syndrome | 2021-12-10 | criteria provided, single submitter | curation | The p.Asn78fs variant in HPS1 has not been previously reported in individuals with Hermansky-Pudlak syndrome but has been identified in 0.0009% (1/113770) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs773323079). 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. This variant has also been reported in ClinVar (Variation ID#: 435451) and has been interpreted as pathogenic by Invitae and Genetic Services Laboratory (University of Chicago). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 78 and leads to a premature termination codon 43 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the HPS1 gene is an established disease mechanism in autosomal recessive Hermansky-Pudlak syndrome. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive Hermansky-Pudlak syndrome. ACMG/AMP Criteria applied: PVS1, PM2 (Richards 2015). |
| Fulgent Genetics, |
RCV000500361 | SCV002797783 | likely pathogenic | Hermansky-Pudlak syndrome 1 | 2022-04-16 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003419860 | SCV004113846 | likely pathogenic | HPS1-related disorder | 2023-05-11 | criteria provided, single submitter | clinical testing | The HPS1 c.233_242del10 variant is predicted to result in a frameshift and premature protein termination (p.Asn78Metfs*43). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-100195404-ATACAGGAAGT-A). Frameshift variants in HPS1 are expected to be pathogenic. Therefore we interpret c.233_242del (p.Asn78Metfs*43) as likely pathogenic. |
| Baylor Genetics | RCV000500361 | SCV004199977 | likely pathogenic | Hermansky-Pudlak syndrome 1 | 2022-05-04 | criteria provided, single submitter | clinical testing |