ClinVar Miner

Submissions for variant NM_024747.5(HPS6):c.238dup (p.Asp80fs) (rs281865108)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000190593 SCV000245620 likely pathogenic Hermansky-Pudlak syndrome 6 2015-02-26 criteria provided, single submitter clinical testing The p.Asp80GlyfsX96 variant in HPS6 has been reported in 1 compound heterozygous individual with clinical features of Hermansky-Pudlak syndrome (Huizing 2009). Data from large population studies is insufficient to assess the frequency of this variant. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 80 and leads to a premature termination codon 96 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Truncating HPS6 variants have been identified in several homozygous and compound heterozygous individuals with Hermansky-Pudlak syndrome (Zhang 2003, Huizing 2009). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic.
NIHR Bioresource Rare Diseases, University of Cambridge RCV000851747 SCV000899618 pathogenic Hermansky-Pudlak syndrome 2019-02-01 criteria provided, single submitter research
Illumina Clinical Services Laboratory,Illumina RCV000190593 SCV000915456 uncertain significance Hermansky-Pudlak syndrome 6 2018-11-14 criteria provided, single submitter clinical testing The HPS6 c.238dupG (p.Asp80GlyfsTer96) variant results in a frameshift and is predicted to result in premature termination of the protein. The p.Asp80GlyfsTer96 variant has been reported in one study in which it is identified in a compound heterozygous state with a missense variant in one individual diagnosed with Hermansky- Pudlak syndrome (Huizing et al. 2009). Control data are unavailable for this variant which is not found in the 1000 Genomes Project, the Exome Sequencing Project, Exome Aggregation Consortium, or the Genome Aggregation Database. Based on the limited clinical evidence and potential impact of frameshift variants, the c.238dupG (p.Asp80GlyfsTer96) variant is classified as a variant of unknown significance but suspicious for pathogenicity for Hermansky-Pudlak syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000190593 SCV000044942 pathogenic Hermansky-Pudlak syndrome 6 2009-12-01 no assertion criteria provided literature only

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