Submissions for variant NM_024747.6(HPS6):c.466_475dup (p.Phe159fs)

gnomAD frequency: 0.00001  dbSNP: rs1462863412

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001987613	SCV002226754	pathogenic	not provided	2023-06-23	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe159Cysfs*20) in the HPS6 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 617 amino acid(s) of the HPS6 protein. This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with HPS6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1443600). This variant disrupts a region of the HPS6 protein in which other variant(s) (p.Leu356Alafs*11) have been determined to be pathogenic (PMID: 17041891). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002243490	SCV002515683	likely pathogenic	Hermansky-Pudlak syndrome 6		no assertion criteria provided	research