Submissions for variant NM_006846.4(SPINK5):c.891C>T (p.Cys297=)

gnomAD frequency: 0.00004  dbSNP: rs752941297

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000415446	SCV000492792	likely pathogenic	Erythroderma; Increased circulating IgE concentration	2015-07-13	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV000788305	SCV000927364	pathogenic	not provided	2017-08-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003595957	SCV000946534	pathogenic	Ichthyosis linearis circumflexa	2024-12-26	criteria provided, single submitter	clinical testing	This sequence change affects codon 297 of the SPINK5 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SPINK5 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or altered protein product. This variant is present in population databases (rs752941297, gnomAD 0.006%). This variant has been observed in individuals with Netherton syndrome (PMID: 22089833, 22377713). It is commonly reported in individuals of Greek ancestry (PMID: 22089833). ClinVar contains an entry for this variant (Variation ID: 374066). Studies have shown that this variant results in skipping of exon 11, and produces a non-functional protein and/or introduces a premature termination codon (PMID: 22089833, 22377713, 25665175). For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000806530	SCV001367772	likely pathogenic	Netherton syndrome	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Likely pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000788305	SCV001762255	pathogenic	not provided	2021-06-17	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000806530	SCV002021945	pathogenic	Netherton syndrome	2020-06-23	criteria provided, single submitter	clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV000806530	SCV005090980	pathogenic	Netherton syndrome	2024-05-16	criteria provided, single submitter	clinical testing	PVS1_strong, PS3, PS4_mod, PM2- The variant is expected to result in an absent or disrupted protein product. It has been reported in ClinVar as Pathogenic by other laboratories (Variation ID: 374066). Low frequency in gnomAD population databases.
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000788305	SCV005198346	pathogenic	not provided	2023-11-23	criteria provided, single submitter	clinical testing
GeneDx	RCV000788305	SCV005201207	pathogenic	not provided	2023-11-29	criteria provided, single submitter	clinical testing	Variant demonstrated to result in abnormal splicing leading to protein truncation in a gene for which loss of function is a known mechanism of disease (PMID: 22377713, 22089833, 25665175); Possible founder variant commonly reported in individuals of Greek ancestry (PMID: 22089833); This variant is associated with the following publications: (PMID: 34426522, 31589614, 34543653, 33534181, 26865388, 32767583, 28289593, 27905021, 25665175, 22089833, 22377713, 33890311, 29159247, 37834063, 28914264)
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	RCV000806530	SCV005413152	pathogenic	Netherton syndrome	2024-04-09	criteria provided, single submitter	clinical testing