Submissions for variant NM_024747.6(HPS6):c.1228_1252del (p.Tyr410fs)

dbSNP: rs760452661

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003094167	SCV002963429	pathogenic	not provided	2023-02-26	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 1691238). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the HPS6 protein in which other variant(s) (p.Pro633LeufsX76) have been determined to be pathogenic (PMID: 27225848). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This premature translational stop signal has been observed in individual(s) with Hermansky-Pudlak syndrome (PMID: 32830442). This variant is present in population databases (rs760452661, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Tyr410Valfs*9) in the HPS6 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 366 amino acid(s) of the HPS6 protein.
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002254224	SCV002525460	likely pathogenic	Hermansky-Pudlak syndrome 6		no assertion criteria provided	research