Submissions for variant NM_024747.6(HPS6):c.335G>A (p.Trp112Ter)

dbSNP: rs2067964057

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003660888	SCV004375972	pathogenic	not provided	2023-05-02	criteria provided, single submitter	clinical testing	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.Gln680*) have been determined to be pathogenic (PMID: 27225848, 29054114). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 996366). This premature translational stop signal has been observed in individual(s) with Hermansky-Pudlak syndrome (PMID: 33878481). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp112*) in the HPS6 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 664 amino acid(s) of the HPS6 protein.
Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	RCV001290773	SCV001478884	likely pathogenic	Hermansky-Pudlak syndrome 6	2020-11-13	no assertion criteria provided	clinical testing