Table 6.
15 rare disruptive variants in 7 recurrently mutated genes.
| Sample | Gene | Chr : Pos | DNA change | Protein change | Zygosity state a | PolyPhen-2 b | SIFT c | ACMG/AMP |
|---|---|---|---|---|---|---|---|---|
| A4 | HNRNPA2B1 | chr7:26232882, Exon 10 | c.953C>T (NM_031243.3) | p.Pro330Leu (NP_112533.1) | HET | D | T | Pathogenic |
| A26 | NUP205 | chr7:135279308, Exon 13 | c.1844G>C (NM_015035.3) | p.Arg615Pro (NP_055950.2) | HET | D | D | Pathogenic |
| A27 | CAPN2 | chr1:223905506, Exon 2 | c.280C>T (NM_001748.5) | p.Arg94Cys (NP_001739.3) | HET | D | D | Pathogenic |
| A12 d | CAPN2 | chr1:223905506, Exon 37 | c.479C>T (NM_001748.5) | p.Thr160Ile (NP_001739.3) | HET | D | D | Pathogenic |
| A11 | WNT16 | chr7:120969800, Exon 2 | c.275G>T (NM_057168.2) | p.Cys92Phe (NP_476509.1) | HET | D | D | Pathogenic |
| A28 | NUP214 | chr9:134004853, Exon 4 | c.581C>T (NM_005085.4) | p.A194Val (NP_005076.3) | HET | P | D | Pathogenic |
| A30 | NUP214 | chr9:134026097, Exon 16 | c.2222G>T (NM_005085.4) | p.Arg741Leu (NP_005076.3) | HET | D | T | Pathogenic |
| A8 e | NUP214 | chr9:134074060, Exon 29 | c.5179G>A (NM_005085.4) | p.Gly1727Arg (NP_005076.3) | HET | D | D | Pathogenic |
| A12 d | RYR3 | chr15:33961612, Exon 50 | c.5677C>T (NM_001036.6) | p.Arg1893Trp (NP_001027.3) | HET | P | D | Pathogenic |
| A8 e | RYR3 | chr15:34030748, Exon 104 | c.7613C>T (NM_001036.6) | p.Thr2538Met (NP_001027.3) | HET | D | D | Pathogenic |
| A29 | RYR3 | chr15:34157399, Exon 37 | c.14585G>A (NM_001036.6) | p.Arg4862His (NP_001027.3) | HET | D | D | Pathogenic |
| A14 | RYR1 | chr19:38993321, Exon 48 | c.7789A>G (NM_000540.3) | p.Lys2597Glu (NP_000531.2) | HET | D | D | Pathogenic |
| A13 | RYR1 | chr19:39006731, Exon 65 | c.9559C>T (NM_000540.3) | p.Arg3187Trp (NP_000531.2) | HET | D | D | Pathogenic |
| A24 | CAPN2 | chr1:223959628, Intron 19 | c.2020+1delG (NM_001748.5) | p.X674_splice (NP_001739.3) | HET | NA | NA | Pathogenic |
| A9 | WNT16 | chr7:120969635, Exon 2 | c.81delC (NM_057168.2) | p.S38Pfs*15 (NP_476509.1) | HET | NA | NA | Pathogenic |
a
Zygosity stats: HET: heterozygous; HO: Homozygous.
b
PolyPhen-2 predictions: B, benign; D, probably damaging; P, possibly damaging.
c
SIFT predictions: D, deleterious; T, tolerated.
d,e
One individual harboring two variants.
NA, not available; ACMG/AMP, the guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.