Description
The SPINK1 c.194+2T>C variant (rs148954387) has been reported in the literature in numerous individuals diagnosed with chronic pancreatitis (Cho 2016, Kume 2006, Witt 2000, Zou 2018) and is one of the most common pathogenic variants in East Asian individuals affected with pancreatitis (Cho 2016, Zou 2018). This variant is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 132142), and it is found in the general population with an overall allele frequency of 0.03% (85/280290 alleles) in the Genome Aggregation Database. This variant abolishes the canonical splice donor site of intron 4, which is likely to disrupt gene function. Indeed, functional studies indicate a significant reduction of mRNA levels, skipping of exon 3, and undetectable levels of the SPINK1 protein (Kereszturi 2009, Kume 2006, Zou 2016). Based on available information, the c.194+2T>C variant is considered to be pathogenic. References: Cho SM et al. PRSS1, SPINK1, CFTR, and CTRC Pathogenic Variants in Korean Patients With Idiopathic Pancreatitis. Ann Lab Med. 2016 Nov;36(6):555-60. Kereszturi E et al. Minigene analysis of intronic variants in common SPINK1 haplotypes associated with chronic pancreatitis. Gut. 2009; 58(4):545-9. Kume K et al. [-215G>A; IVS3+2T>C] mutation in the SPINK1 gene causes exon 3 skipping and loss of the trypsin binding site. Gut. 2006; 55(8):1214. Witt H et al. Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis. Nat Genet. 2000; 25(2):213-6. Zou WB et al. Clarifying the clinical relevance of SPINK1 intronic variants in chronic pancreatitis. Gut. 2016 May;65(5):884-6. Zou WB et al. SPINK1, PRSS1, CTRC, and CFTR Genotypes Influence Disease Onset and Clinical Outcomes in Chronic Pancreatitis. Clin Transl Gastroenterol. 2018 Nov 12;9(11):204.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
