Submissions for variant NM_003978.5(PSTPIP1):c.1054G>A (p.Glu352Lys)

gnomAD frequency: 0.00012  dbSNP: rs201186216

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000269627	SCV000394012	benign	Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV001718657	SCV000589351	likely benign	not provided	2020-09-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000269627	SCV000764078	likely benign	Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	2024-01-11	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000269627	SCV001472995	uncertain significance	Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	2022-04-08	criteria provided, single submitter	clinical testing	The PSTPIP1 c.1054G>A; p.Glu352Lys variant (rs201186216) is reported in the literature in an individual affected with systemic auto-inflammatory disease (Rusmini 2016) but the variant was not determined to be causative. This variant is also reported in ClinVar (Variation ID: 317183) and is found in the general population with an allele frequency of 0.03% (83/277034 alleles) in the Genome Aggregation database. The glutamic acid at codon 352 is weakly conserved, and computational analyses predict that this variant is neutral (REVEL: 0.078). Due to limited information, the clinical significance of the p.Glu352Lys variant is uncertain at this time. Reference: Rusmini M et al. Next-generation sequencing and its initial applications for molecular diagnosis of systemic auto-inflammatory diseases. Ann Rheum Dis. 2016 Aug;75(8):1550-7. PMID: 26386126.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002263003	SCV002542442	likely benign	Autoinflammatory syndrome	2021-05-25	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001718657	SCV004137431	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	PSTPIP1: BP4, BS2
PreventionGenetics, part of Exact Sciences	RCV003910199	SCV004718688	likely benign	PSTPIP1-related disorder	2023-08-01	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).