Submissions for variant NM_024747.6(HPS6):c.206_210dup (p.Trp71fs)

dbSNP: rs2136333791

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001358142	SCV001553802	likely pathogenic	Hermansky-Pudlak syndrome 6		no assertion criteria provided	clinical testing	The HPS6 p.Trp71Glyfs*158 variant was not identified in the literature nor was it identified in dbSNP, ClinVar, Cosmic, LOVD 3.0 or in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The c.206_210dup variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 71 and leads to a premature stop codon at 158 amino acids downstream. This alteration is then predicted to result in a truncated or absent protein and loss of function. Loss of function variants of the HPS6 gene are an established mechanism of disease in Hermansky-Pudlak syndrome 6 and is the type of variant expected to cause the disorder when found in the homozygous or compound heterozygous state. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic.