# Multiple Genetic Rare Variants in Autism Spectrum Disorders: A Single-Center Targeted NGS Study
## 3 Results
### Variants Already Associated with Autism
\begin{table}
\begin{tabular}{c c c c c c c} \hline \hline \multirow{2}{*}{**Gene**} & **SFARI** & \multirow{2}{*}{**Variant**} & **Chr Position** & \multirow{2}{*}{**Predictions (S-P)**} & \multirow{2}{*}{**GnomAD**} & \multirow{2}{*}{**Patient**} & \multirow{2}{*}{**Transmission**} \\  & **Score** & & **(GRCh37)** & & & \\ \hline \multirow{2}{*}{NSD1} & \multirow{2}{*}{S} & c.7367T>C; & 5:176,721,736 & S deleterious–low confidence, P benign & 0.00006 & \multirow{2}{*}{F14/70} & \multirow{2}{*}{Maternal} \\  & & p.Met2456 Thr & & & & & \\ \hline \multirow{2}{*}{SCN2A} & \multirow{2}{*}{1} & c.2723A>G; & \multirow{2}{*}{2:166,201,225} & S tolerated, P possibly damaging & \multirow{2}{*}{0.004 (1/250)} & \multirow{2}{*}{C.L.} & \multirow{2}{*}{Unknown} \\  & & p.Lys908 Arg & & & & & \\ \hline \multirow{2}{*}{CEP290} & \multirow{2}{*}{S} & c.6401T>C; & \multirow{2}{*}{12:88,454,728} & S damaging, P probably damaging & \multirow{2}{*}{0.007 (1/150)} & \multirow{2}{*}{G14/62} & \multirow{2}{*}{Maternal} \\  & & p.Ile2134 Thr & & & & & N13/03 & \\ \hline \multirow{2}{*}{VPS13B} & \multirow{2}{*}{S} & c.2485G>A; & \multirow{2}{*}{8:100,205,255} & \multirow{2}{*}{S tolerated, P benign} & 0.0085 & \multirow{2}{*}{D15/81} & \multirow{2}{*}{Paternal} \\  & & p.Ala829 Thr & & & & & \\ \hline \multirow{2}{*}{RAI1} & \multirow{2}{*}{3S} & c.1142C>T; & \multirow{2}{*}{17:17,697,404} & \multirow{2}{*}{S deleterious, P benign} & \multirow{2}{*}{0.004 (1/250)} & \multirow{2}{*}{r.g.74126} & \multirow{2}{*}{Paternal} \\  & & p.Ala381 Val & & & & & a.d.81815 & \\ \hline \multirow{2}{*}{ZEB2} & \multirow{2}{*}{/} & c.2230A>G; & \multirow{2}{*}{2:145,156,524} & \multirow{2}{*}{S tolerated, P benign} & \multirow{2}{*}{0.002 (1/500)} & \multirow{2}{*}{r.g.74126} & \multirow{2}{*}{Paternal} \\  & & p.Ile744 Val & & & & a.d.81815 & \\ \hline \hline \end{tabular}
\end{table} 
Table 7: Variants shared by two or three patients in our cohort. CACNA1H (AF 0.5%), all of which were inherited from the father, and one extremely rare variant in MET (AF 0.002%), inherited from the mother. The variant, c.2941G\(>\)A (p.Ala981 Thr), in the CREBBP gene was first identified in a study conducted on a cohort of patients affected by Rubinstein-Taybi syndrome (RTS) [32]. In our study, we found this variant in one patient (D10/14), together with two other variants that are not extremely rare in the VPS13B gene (AF 0.17% and 0.045%), but it was not possible to study the family segregation to establish if they are on the same allele or not. The variant, c.1886G\(>\)A (p.Ser629 Asn), in the SLIT3 gene was identified in two ASD families in a whole-exome sequencing study, as described by [PERSON] et al. [23]. In our study, p.Ser629 Asn was found in one patient (L14/95) as a de novo variant, together with two not extremely rare variants (in MBD5, AF 0.2%; and VPS13B, AF 0.3%) and two more rare variants (in ANK2, AF 0.07%; and KDM6B, AF 0.02), all maternally inherited. The variant, c.12653A\(>\)G (p.Asp4218 Gly), in the FAT1 gene was first identified in one family in the same study by [PERSON] et al. [23], previously cited for the SLIT3 variant. In our study, we identified one patient (r.g.74126) carrying p.Asp4218 Gly (maternally inherited), together with an additional three frequent variants, two of which were inherited from the father (in ZEB2, AF 0.2%; and RAI1, AF 0.4%) and one from the mother (in CSMD1, AF 0.6%), and one more rare variant inherited from the mother (in AVPR1A, 0.09%). The variant, c.1960C\(>\)G (p.Gln654 Glu), in the TSC1 gene was first identified in a study by [PERSON] et al. [33]. In our cohort, we found this variant in one patient ([PERSON]), carried by the maternal allele, together with one additional variant in LAMC3 (AF 0.02). In the same individual, we found, on the paternal allele, two not extremely rare variants in ANKRD11 (AF 0.04%) and a more frequent one in KATNAL2 (AF 0.1%).