Submissions for variant NM_006846.4(SPINK5):c.1431-12G>A

dbSNP: rs368134354

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000414252	SCV000490828	pathogenic	not provided	2023-03-11	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26762237, 21255986, 26229701, 19683336, 22089833, 15304086, 29444371, 28289593, 31589614, 32441320)
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000414954	SCV000492793	likely pathogenic	Erythroderma; Increased circulating IgE concentration	2015-07-13	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000414252	SCV001249574	pathogenic	not provided	2024-10-01	criteria provided, single submitter	clinical testing	SPINK5: PM3:Very Strong, PM2
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000766268	SCV001367773	likely pathogenic	Netherton syndrome	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003595955	SCV001590575	pathogenic	Ichthyosis linearis circumflexa	2024-10-28	criteria provided, single submitter	clinical testing	This sequence change falls in intron 15 of the SPINK5 gene. It does not directly change the encoded amino acid sequence of the SPINK5 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individuals with Netherton syndrome (PMID: 15304086, 21255986, 26229701, 28289593). It has also been observed to segregate with disease in related individuals. This variant is also known as 1432-13 G>A. ClinVar contains an entry for this variant (Variation ID: 372516). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects SPINK5 function (PMID: 15304086, 21255986). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000766268	SCV002797269	pathogenic	Netherton syndrome	2022-03-29	criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000414252	SCV005198347	pathogenic	not provided	2023-11-23	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn	RCV000766268	SCV005413153	likely pathogenic	Netherton syndrome	2024-04-09	criteria provided, single submitter	clinical testing
OMIM	RCV000766268	SCV000897725	pathogenic	Netherton syndrome	2019-04-08	no assertion criteria provided	literature only