Submissions for variant NM_006846.4(SPINK5):c.802C>T (p.Arg268Cys)

gnomAD frequency: 0.00581  dbSNP: rs142558269

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000385948	SCV000453745	likely benign	Netherton 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514631	SCV000610191	likely benign	not provided	2017-06-12	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003761917	SCV000631310	benign	Ichthyosis linearis circumflexa	2025-02-03	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000385948	SCV000743991	benign	Netherton syndrome	2014-10-09	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000385948	SCV000745451	likely benign	Netherton syndrome	2017-11-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000514631	SCV001154540	likely benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	SPINK5: BP4, BS2
GeneDx	RCV000514631	SCV001941743	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000385948	SCV002795290	likely benign	Netherton syndrome	2022-03-18	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000514631	SCV005228206	likely benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000385948	SCV000734386	likely benign	Netherton syndrome		no assertion criteria provided	clinical testing
Santos-Cortez Lab, University of Colorado School of Medicine	RCV001260959	SCV001338937	uncertain significance	Susceptibility to nonsyndromic otitis media	2020-04-18	no assertion criteria provided	research
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000514631	SCV001798807	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003922548	SCV004743642	benign	SPINK5-related disorder	2023-10-04	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).