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Table 3 Deleterious sequence variants identified in patients with ASD in day-care hospitals of the Greater Paris region

From: Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder

Patient Method Gene Reference sequence cDNA and protein changes Zygosity Mode of inheritance Sex ACMG classificationa Evidence Phenotype (MIM number)
35 ASD/ID panel ADNP NM_015339 c.2499del, p.Val834Serfs*80 Heterozygous De novo M Pathogenic (Ia) PVS1, PS2, PM2 Helsmoortel van der Aa syndrome (615873)
36 ASD/ID panel ADNP NM_015339 c.517C>T, p.Arg173* Heterozygous De novo M Pathogenic (Ia) PVS1, PS2, PM2 Helsmoortel van der Aa syndrome (615873)
37 ASD/ID panel ANKRD11 NM_013275 c.3542_3543ins23, p.Arg1182Alafs*144 Heterozygous De novo M Pathogenic (Ia) PVS1, PS2, PM2 KBG syndrome (148050)
38 ASD/ID panel ARID1B NM_020732.3 c.4110G>A, p.His1339Ilefs*77 (b) Heterozygous De novo M Pathogenic (Ia) PVS1, PS2, PS1, PM2 Coffin-Siris syndrome 1 (135900)
39 WES ATRX NM_000489.3 c.6740A>C, p.His2247Pro Hemizygous Inherited from heterozygous mother M Likely pathogenic (II) PS1, PM2, PP2, PP3, PP4 Mental retardation-hypotonic facies syndrome, X-linked (309580)
40 WES CACNA1E NM_000721.3 c.4688A>G, p.Lys1563Arg Heterozygous De novo M Likely pathogenic (II) PS2, PM2, PP2, PP3 Epileptic encephalopathy, early infantile, 69 (618285)
41 WES CHD2 NM_001271.3 c.2352+1G>A, p.Lys730Asnfs*4 Skip of exon 18 Heterozygous De novo M Pathogenic (Ia) PVS1, PS2, PM2 Epileptic encephalopathy, childhood-onset (615369)
42 WES COG4 NM_015386.2 c.15G>A, p.Met5Ile Homozygous Inherited from heterozygous parents M Likely pathogenic (V) PM2, PM3, PP2, PP3, PP4 Congenital disorder of glycosylation, type IIj (613489)
43 WES FOXP1 NM_032682.5 c.1541G>A, p.Arg514His Heterozygous De novo F Likely pathogenic (II) PS2, PM2, PP2, PP3 Mental retardation with language impairment and with or without autistic features (613670)
44 ASD/ID panel FOXP1 NM_032682.5 c.1541G>A, p.Arg514His Heterozygous De novo F Likely pathogenic (II) PS2, PM2, PP2, PP3 Mental retardation with language impairment and with or without autistic features (613670)
45 WES GNAO1 NM_020988.2 c.736G>A, p.Glu246Lys Heterozygous De novo F Pathogenic (II) PS2, PS1, PM2, PP2, PP3, PP4 Epileptic encephalopathy, early infantile 17 (615473)
46c ASD/ID panel GRIA3 NM_000828 c.504del, p.Glu168Aspfs*21 Hemizygous Inherited from mother with somatic mosaicism M Pathogenic (Ib) PVS1, PM2, PP1-M Mental retardation, X-linked 94 (300699)
47c ASD/ID panel GRIA3 NM_000828 c.504del, p.Glu168Aspfs*21 Hemizygous Inherited from mother with somatic mosaicism M Pathogenic (Ib) PVS1, PM2, PP1-M Mental retardation, X-linked 94 (300699)
48 ASD/ID panel GRIA3 NM_000828 c.1990C>G, p.Pro664Ala Hemizygous Inherited from heterozygous mother M Likely pathogenic (II) PS1, PM2, PP2, PP3, PP4 Mental retardation, X-linked 94 (300699)
49 ASD/ID panel GRIN2B NM_000834.4 c.2087G>A, p.Arg696His Heterozygous De novo F Pathogenic (II) PS2, PS1, PM2, PP2, PP3, PP4 Mental retardation, autosomal dominant 6 (613970)
50 ASD/ID panel GRIN2B NM_000834.4 c.2084T>C, p.Ile695Thr Heterozygous De novo M Pathogenic (II) PS2, PS1, PM2, PP2, PP3, PP4 Mental retardation, autosomal dominant 6 (613970)
51 ASD/ID panel HUWE1 NM_031407.6 c.1736A>C, p.Asn579Thr Hemizygous Inherited from heterozygous mother M Likely pathogenic (II) PS1, PM2, PP2, PP3, PP4 Mental retardation, X-linked syndromic (300706)
52 Epilepsy panel IQSEC2 NM_001111125.2 c.2272C>T, p.Arg758* Heterozygous de novo F Pathogenic (Ia) PVS1, PS2, PM2 Mental retardation, X-linked 78 (309530)
53 WES KCNB1 NM_004975.2 c.128A>G, p.Glu43Gly Heterozygous De novo M Likely pathogenic (II) PS2, PM2, PP3, PP2 Epileptic encephalopathy, early infantile 26 (616056)
54 ASD/ID panel KDM6A NM_021140.3 c.2944G>T, p.Gly982* Heterozygous De novo M Pathogenic (Ia) PVS1, PS2, PM2 Kabuki syndrome 2 (300867)
55 WES LINS1 NM_001040616.2 c.1921del, p.Glu641Serfs*4 Homozygous Inherited from heterozygous parents M Likely pathogenic (V) PM2, PM3, PP2, PP3, PP4 Mental retardation, autosomal recessive 27 (614340)
56 ASD/ID panel MED13L NM_015335.4 c.1708_1709del, p.Ser570Phefs*27 Heterozygous De novo F Pathogenic (Ia) PVS1, PS2, PM2 Mental retardation and distinctive facial features with or without cardiac defects (616789)
57 ASD/ID panel MYT1L NM_015025.3 c.1579G>C, p.Gly527Arg Heterozygous De novo F Pathogenic (II) PS2, PS1, PM2, PP2, PP3, PP4 Mental retardation, autosomal dominant 39 (616521)
58 ASD/ID panel NAA10 NM_003491.3 c.236G>A, p.Arg79His Heterozygous De novo M Likely pathogenic (II) PS2, PM2, PP2, PP3 Ogden syndrome (300855)
59 WES PHF6 NM_032458.2 c.385C>T, p.Arg129* Heterozygous De novo F Pathogenic (Ia) PVS1, PS2, PM2 Borjeson-Forssman-Lehmann syndrome (301900)
60 WES, Epilepsy panel RORB NM_006914.3 c.640C>T, p.Arg214* Heterozygous De novo F Pathogenic (Ia) PVS1, PS2, PM2 Epilepsy, idiopathic generalized, susceptibility to, 15 (618357)
61 ASD/ID panel SHANK3 NM_033517.1 c.5021G>A, p.Gly1674Asp Heterozygous Inherited from the affected mother M Likely pathogenic (II) PP1-S, PM2, PP2, PP3, PP4 Phelan-McDermid syndrome (606232)
62 ASD/ID panel SHANK3 NM_033517.1 c.3679dup, p.(Ala1227Glyfs*69) Heterozygous De novo M Pathogenic (Ia) PVS1, PS2, PM2 Phelan-McDermid syndrome (606232)
63 ASD/ID panel SLC6A1 NM_003042 c.752T>C, p.Leu251Pro Heterozygous De novo F Likely pathogenic (II) PS2, PM2, PP3, PP2 Myoclonic-atonic epilepsy (616421)
64 Epilepsy panel STXBP1 NM_003165.3 c.87+1G>T, p.? Heterozygous De novo M Pathogenic (Ia) PVS1, PS2, PM2 Epileptic encephalopathy, early infantile, 4 (612164)
65 ASD/ID panel SZT2 NM_015284.3 c.1261+1G>A, p.? c.6113A>G, p.Tyr2038Cys Compound heterozygous Inherited from heterozygous parents F Likely pathogenic (V) PVS1, PM2, PM3, PP2, PP3, PP4 Epileptic encephalopathy, early infantile 18 (615476)
66 ASD/ID panel TLK2 NM_006852.3 c.1015C>T, p.Arg339Trp Heterozygous De novo M Pathogenic (II) PS2, PS1, PM2, PP2, PP3, PP4 Mental retardation, autosomal dominant 57 (618050)
67 WES TUSC3 NM_006765.3 c.787_788insC, p.Asn263Thrfs* homozygous Inherited from heterozygous parents M Pathogenic (Ib) PVS1, PM2, PM3, PP2 Mental retardation, autosomal recessive 7 (611093)
  1. ASD autism spectrum disorder, F female, ID intellectual disability, M male, WES whole exome sequencing
  2. aVariants were assessed for pathogenicity according to the American College of Medical Genetics and Genomics (ACMG) criteria [7]
  3. bIn patient 38, the c.4110G>A variant in ARID1B is predicted to result in a synonymous substitution (p.Pro1370=) in the last base pair of exon 17. Further studies indicated that this variant affects the splice donor site and induces skipping of exon 17, causing a frameshift and premature termination (p.His1339Ilefs*77) [16]
  4. cPatients 46 and 47 are siblings