Supplementary table 1a.PHKA2 variants predicted to be pathogenic and likely pathogenic, based on the American College of Medical Genetics Criteria, identified in our study cohort (Patients 1-12) and from analysis of a further 24 families.
Location / cDNA change / amino acid change / ReferencesExon 2 / c.133C>T / p.Arg45Trp / (Davit-Spraul et al 2011; Tsilianidis et al 2013; Wang et al 2013; Brown et al 2015), Patients 1 and 2
Exon 2 / c.134G>A / p.Arg45Gln / Patient 3
Intron 5 / c.537+2T>C / intronic / Patient 4, (c.537+5G>A reported (Davit-Spraul et al 2011; Choi et al 2016)
Exon 6 / c.556C>T / p.Arg186Cys / (Hendrickx et al 1996; Hendrickx et al 1999; Davit-Spraul et al 2011)
Exon 6 / c.557G>A / p.Arg186His / (Burwinkel et al 1996; Hendrickx et al 1998; Hendrickx et al 1999; Roscher et al 2014)
Exon 8 / c.811delG / p.Glu271Lysfs*3 / Patient 5
Exon 9 / c.883C>T / p.Arg295Cys / (Ban et al 2003; Tsilianidis et al 2013), Patients 6 and 7
Exon 9 / c.884G>A / p.Arg295His / (Hendrickx et al 1999; Choi et al 2016), Patient 8
Exon 12 / c.1205G>A / p.Trp402* / This study
Intron 13-20 / c.1324+533_2227-1762del / This study
Intron 16 / c.1715-2A>G / intronic / Patient 9
Exon 21 / c.2337dupT / p.Leu780Serfs*30 / This study
Exon 21 / c.2238_2239delTG insGAACAGGCC / p.Ser746Argfs*11 / Patient 10
Exon 23 / c.2593delT / p.Ser865Leufs*49 / This study
Exon 31 / c.3334G>T / p.Glu1112* / Patient 11
Exon 32 / c.3440dupT / p.Thr1148Aspfs*55 / This study
Exon 33 / c.3614C>T / p.Pro1205Leu / (van den Berg et al 1995; Hirono et al 1998; Achouitar et al 2011; Davit-Spraul et al 2011; Roscher et al 2014; Choi et al 2016), Patient 12
Supplementary table 1b.PHKA2 variants of unknown clinical significance (VOUS), based on the American College of Medical Genetics Criteria, identified in our study cohort (Patients 1-12) and from analysis of a further 24 families.
Location / cDNA change / amino acid change / Referencesexon 4 / c.301_303delAAG / p.Lys101del / This study
Exon 7 / c.708G>C / p.Glu236Asp / This study
Exon 8 / c.749C>T / p.Ser250Leu / This study
Exon 12 / c.1215C>T / p.Ser405Ser / This study
Exon 15 / c.1493C>T / p.Pro498Leu / (Beauchamp et al 2007)
Exon 16 / c.1576G>A / p.Asp526Asn / This study
Exon 16 / c.1712T>C / p.Leu571Pro / This study
Intron 18 / c.1963+3A>G / This study
Exon 33 / c.3629G>A / p.Gly1210Glu / (Rudolfova et al 2001)
Supplementary table 1c.PHKA2 variants predicted to be likely benign or benign, based on the American College of Medical Genetics Criteria, identified in our study cohort (Patients 1-12) and from analysis of a further 24 families.
Location / cDNA change / amino acid change / rs number / Minor allele frequency (ExAC)Intron 7 / c.718-3C>T / intronic / rs151344532 / 0.01092
Exon 2 / c.112G>C / p.Glu38Gln / rs17313469 / 0.01985
Exon 18 / c.1952C>A / p.Thr651Asn / rs149991825 / 0.00497
Exon 19 / c.2077A>G / p.Ile693Val / rs143732206 / 0.008308
Intron 21 / c.2361-12A>C / rs148877451 / 0.01041
Exon 22 / c.2436G>A / p.Gly812Gly / rs61733281 / 0.007532
References
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