Table 4.
Highlighted Mosaic Mutations in Candidate ASD Risk Genes
| Person:Sex | NVIQ/VIQ | Gene | Func | Gene Lista |
SSC Pro GDM Counta |
SSC Sib GDM Counta |
AF | HGVSc | HGVSp | Pub | Other Pub NS GDM | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| LGD | Mis | LGD | Mis | ||||||||||
| 13073.p1:M | 60/25 | CHD2 | mis | HC11, 32, 40 | 3 | 0 | 0 | 0 | 14/125 (11%) | NM_001042572.2; c.272A>G | p.Glu91Gly | N | SYNGAP1:fs del |
| 12139.p1:M | 106/86 | CTNNB1 | mis | HC40 | 1 | 1 | 0 | 0 | 8/103 (8%) | NM_001098209.1; c.1127G>A | p.Arg376His | N | GPBP1:mis |
| 14687.p1:M | 38/62 | INTS6 | ns | HC40 | 0 | 0 | 0 | 0 | 13/54 (24%) | NM_001039937.1; c.1789C>T | p.Arg597Ter | Y | ATP2A1:mis |
| 12028.p1:M | 93/80 | KIF1A | mis | HC40 | 0 | 1 | 0 | 1 | 29/250 (12%) | NM_001244008.1; c.655G>A | p.Ala219Thr | N | NA |
| 11305.p1:M | 35/60 | KANSL1 | mis | HC40 | 0 | 0 | 0 | 0 | 40/126 (32%) | NM_001193465.1; c.729A>C | p.Gln243His | Yb | OR1S1:misc |
| 11592.p1:M | 109/122 | KAT2B | sp | HC32 | 0 | 0 | 0 | 0 | 20/80 (25%) | NM_003884.4; c.1151−1G>A | – | Yb | NA |
| 13897.p1:M | 91/78 | KMT2C | mis | HC32, 40 | 1 | 1 | 0 | 0 | 8/115 (7%) | NM_170606.2; c.14416C>G | p.Arg4806Gly | N | CGGBP1:mis |
| 13522.mo:Md | 87/70 | SCN2A | mis | HC11, 32, 40 | 2 | 4 | 0 | 0 | 11/50 (22%) | NM_001040142.1; c.3370A>T | p.Ser1124Cys | N | NA |
| 14001.p1:M | 63/38 | SYNGAP1 | mis | HC11, 32, 40 | 1 | 1 | 0 | 0 | 18/74 (24%) | NM_006772.2; c.3055C>T | p.Arg1019Cys | Yb | NA |
| 12335.p1:F | 47/66 | TBL1XR1 | mis | HC40 | 1 | 0 | 0 | 0 | 9/40 (22%) | NM_024665.4; c.845T>C | p.Leu282Pro | Yb | STK36:mis; SPATA32:mis |
| 13012.p1:M | 60/21 | DIP2A | fs ins | HC11, 32, 40 | 1 | 0 | 0 | 0 | 34/164 (21%) | NM_001146114.1; c.1646_1652dup7 | p.Leu552ValfsTer34 | Ye | RELN:mis |
| 11232.p1:M | 68/91 | GIGYF1 | fs del | HC32 | 2 | 0 | 0 | 0 | 15/65 (23%) | NM_022574.4; c.1140_1156del17 | p.Thr381ArgfsTer13 | Ye | NA |
| 13694.p1:M | 26/17 | BAZ2B | ns | GLGD | 1 | 0 | 0 | 1 | 9/163 (6%) | NM_013450.2; c.3868C>T | p.Arg1290Ter | N | NA |
| 11411.fa:Md | 67/51 | COL5A3 | mis | GLGD | 1 | 0 | 0 | 0 | 16/68 (24%) | NM_015719.3; c.3338C>T | p.Pro1113Leu | N | SNRK:mis; TSNARE1:mis |
| 14051.p1:M | 115/107 | CTNNA3 | mis | GLGD | 1 | 0 | 0 | 0 | 9/295 (3%) | NM_001127384.1; c.152G>C | p.Arg51Pro | N | SEC16B:mis; RFC5:mis |
| 12120.p1:M | 115/85 | SPEN | mis | GLGD | 1 | 1 | 0 | 0 | 15/58 (26%) | NM_015001.2; c.4651G>A | p.Glu1551Lys | Y | OR5J2:mis |
| 14420.p1:M | 101/80 | SSPO | mis | GLGD | 1 | 1 | 0 | 0 | 29/98 (30%) | NM_198455.2; c.14150C>G | p.Ala4717Gly | Y | SH3BP5L:mis; ZMIZ2:mis |
| 14547.p1:M | 95/60 | UNC79 | ns | GLGD | 1 | 0 | 0 | 0 | 9/106 (8%) | NM_020818.3; c.6208C>T | p.Arg2070Ter | N | UQCRC2:mis |
| 12025.p1:M | 96/69 | USP15 | ns | GLGD | 1 | 0 | 0 | 0 | 8/164 (5%) | NM_001252078.1; c.813T>G | p.Tyr271Ter | N | NA |
| 12837.p1:M | 92/89 | BIRC6 | mis | GMIS | 0 | 1 | 0 | 2 | 23/123 (19%) | NM_016252.3; c.9578G>C | p.Arg3193Pro | Y | SH3RF3:mis |
| 13215.p1:M | 69/87 | CFAP74 | mis | GMIS | 0 | 1 | 0 | 0 | 8/157 (5%) | NM_001080484.1; c.1127G>A | p.Arg376Lys | N | JUP:mis |
| 11942.p1:M | 44/62 | DMXL2 | mis | GMIS | 0 | 2 | 0 | 0 | 19/256 (7%) | NM_001174116.1; c.3455A>G | p.Asp1152Gly | N | NA |
| 14248.p1:F | 83/94 | DNAH10 | mis | GMIS | 0 | 2 | 0 | 0 | 13/125 (10%) | NM_207437.3; c.3599G>A | p.Arg1200His | Y | MYO1E:mis; ELAVL2:fs del; ITGA2B:mis |
| 11627.p1:M | 100/83 | DNAH17 | mis | GMIS | 0 | 2 | 0 | 1 | 11/77 (14%) | NM_173628.3; c.7979C>T | p.Ser2660Phe | Y | RGMA:mis |
| 11521.p1:M | 101/128 | MTUS1 | ns | GMIS | 0 | 1 | 0 | 0 | 17/111 (15%) | NM_001001924.2; c.707C>G | p.Ser236Ter | Y | HERC2:misc |
| 14168.p1:M | 140/123 | OBSCN | mis | GMIS | 0 | 2 | 0 | 0 | 14/61 (23%) | NM_001098623.2; c.18344G>A | p.Arg6115Gln | Y | FCGBP:misc |
| 11947.p1:M | 33/28 | SSRP1 | ns | GMIS | 0 | 1 | 0 | 0 | 13/143 (9%) | NM_003146.2; c.159G>A | p.Trp53Ter | N | MDM2:mis; CCR7:mis |
| 13793.p1:M | 56/48 | SYNE1 | mis | GMIS | 0 | 2 | 0 | 1 | 13/225 (6%) | NM_033071.3; c.2330C>T | p.Ala777Val | N | PCDHB4:misc; SBF1:mis |
| 12108.p1:M | 63/74 | VPS13D | ns | GMIS | 0 | 1 | 0 | 0 | 11/133 (8%) | NM_015378.2; c.10552C>T | p.Arg3518Ter | N | KAT6A:fs del; SMG6:mis |
| 14059.p1:M | 105/89 | ACTL6B | syn | novel | 0 | 0 | 0 | 0 | 8/212 (4%) | NM_016188.4; c.360C>T | p.Ser120 = | N | NA |
| 11506.p1:F | 92/82 | COL5A3 | syn | GLGD | 1 | 0 | 0 | 0 | 25/356 (7%) | NM_015719.3; c.2460G>A | p.Ser820 = | N | PSMB4:mis; KIAA17:mis; INPP5D:mis |
| 11115.p1:F | 46/19 | CCT6B | syn | GMIS | 0 | 1 | 0 | 0 | 13/179 (7%) | NM_001193529.1; c.885C>T | p.Ala295 = | N | NA |
| 11336.p1:M | 124/114 | FYN | syn | novel | 0 | 0 | 0 | 0 | 8/129 (6%) | NM_002037.5; c.1051C>T | p.Leu351 = | N | DXO:mis; SLC26A5:mis |
| 14471.p1:M | 96/96 | STMN1 | syn | novel | 0 | 0 | 0 | 0 | 7/90 (8%) | NM_001145454.1; c.219T>C | p.Ala73 = | N | NA |
Abbreviations are as follows: NVIQ, nonverbal IQ; VIQ, verbal IQ; mis, missense; ns, nonsense; syn, synonymous; sp, canonical splicing site; fs, frameshifting mutation; ins, insertion; del, deletion; SSC, Simons Simplex Collection; Pro, proband; Sib, sibling; LGD, likely gene disrupting; GDM, germline de novo mutation; GLGD, overlaps gene with germline LGD mutation; GMIS, overlaps gene with germline missense mutation; HC, overlaps high-confidence risk gene list; AF, allele fraction; HGVSc, Human Genome Variation Society format cDNA; HGVSp, Human Genome Variation Society format protein; Pub, published in de novo mutation calls; NS, nonsynonymous.
Lists and counts compiled after re-classification of published calls (binomial p ≤ 0.001, see Table S2).
Call did not meet 45× joint coverage threshold.
Published GDM call in segmental duplication or tandem repeat loci.
Phenotypic data is for proband.
Indels were identified from re-classification of published calls.