Toward a clinical diagnostic pipeline for SPINK1 intronic variants

Table 2 Rare proximal SPINK1 intronic variants found in French pancreatitis patients

Region	Variant^a		Allele frequency in the European (non-Finnish) population^b	rs number	In silico prediction^c	In vitro validation
Region	cDNA numbering	gDNA numbering (chr5, hg19)	Allele frequency in the European (non-Finnish) population^b	rs number	In silico prediction^c	In vitro validation
Intron 2	c.87 + 13 T > G	g.147209149A > C	Absent from genomAD	Not available	No effect	Yes
Intron 2	c.88-48C > A	g.147207739G > T	0.00001	rs753830042	No effect	Yes
Intron 3	c.194 + 5G > A	g.147207580C > T	Absent from genomAD	Not available	Significantly reduced the score for the c.194 + 2 splice site	Yes
Intron 3	c.194 + 32 T > C	g.147207553A > G	0.00000^d	rs770552173	No effect	Not done
Intron 3	c.195-21 T > A	g.147204290A > T	0.00014	rs377350168	No effect	Not done

^aEach variant was found once in some 4000 patients subjected to routine analysis of the SPINK1 gene. None of the variants have been described in the Genetic Risk Factors in Chronic Pancreatitis Database [6] (as of October 29, 2018)
^bData in accordance with genomAD (as of October 31, 2018)
^cEffect on splice site selection as predicted by SpliceSiteFinder-like, MaxEntScan, NNSPLICE and GeneSplicer under default conditions
^dAbsent in the European (non-Finnish) population but present in other population(s)