Table 2.
Variants identified and associated ACMG pathogenicity classification.
| ID | Age Group | Sex | Gene | Genomic coordinates (hg19) | Reference sequence | cDNA position | Variant | Inheritance | Variant Type | Previously Reported | MAF | ACMG Classification | ACMG Evidence | Detection Method | Accredited Laboratory Classification | ClinVar Accession |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Adult | F | DYNC1H1 | chr14:102446800 | NM_001376.5 | c.874 C > T | p.(R292W) | De novo | SNV | No | 0 | Likely pathogenic (II) | PS2, PM2, PP2, PP3 | In-house | Pathogenic | SCV001027104 |
| 5 | Adult | F | ALDH5A1 | chr6:24505099 & chr6:24528285 | NC_000006.11 | c.[612 G > A];[1273 C > T] | p.(W204*);p.(R412*) | Comp Het | Stopgain / Stopgain | Yes | 0.0002/0.0001 | Pathogenic (Ic) / Pathogenic (Ic) | PVS1, PM3, PP5 & PVS1, PM3, PP5 | In-house | Known pathogenic | SCV001160778 and SCV001160779 |
| 9 | Adult | M | CHD2 | chr15:93563256 | NC_000015.9 | c.4921 C > T | p.(Q1641*) | De novo | Stopgain | Yes | 0 | Pathogenic (Ia) | PVS1,PS2,PM2, PP2, PP5 | In-house | Pathogenic | SCV001160780 |
| 25 | Adult | F | DCX | chrX:110653416 | NC_000023.10 | c.211 G > A | p.(A221V) | De novo | SNV | No | 0 | Pathogenic (IIIb) | PS2, PM2, PM5, PP2, PP3 | In-house | Probably pathogenic | SCV001160781 |
| 30 | Adult | M | CHD2 | chr15:93534746 | NC_000015.9 | c.3454 C > T | p.(R1152W) | De novo | SNV | No | 0 | Likely pathogenic (II) | PS2, PM2,PP2, PP3 | In-house | Unknown significance | SCV001160782 |
| 34 | Adult | M | PURA | chr5:139494545 | NC_000005.9 | c.779 C > G | p.(P260R) | De novo | SNV | No | 0 | Likely pathogenic (II) | PS2, PM2,PP2, PP3 | In-house | Probably pathogenic | SCV001160782 |
| 37 & 39 | Adult | M | MBD5 | chr2:149226238 | NC_000002.11 | c.726delC | p.(D242fs) | Mother | FS Deletion | No | 0 | Pathogenic (Ic) | PVS1, PM2 | In-house | Pathogenic | SCV001160783 |
| 42 | Pead | M | SCN1A | chr2:166915102 | NC_000002.11 | c.361 G > C | p.(A121P) | De novo | SNV | No | 0 | Likely pathogenic (II) | PS2, PM2, PP2, PP3 | In-house | Probably pathogenic | SCV001160784 |
| 43 | Pead | F | STXBP1 | chr9:130435456 | NC_000009.11 | c.1030_1030del | p.(Y344fs) | De novo | FS Deletion | No | 0 | Pathogenic (Ia) | PVS1, PM2, PP3 | In-house | Probably pathogenic | SCV001160785 |
| 50 | Adult | F | GABRA1 | chr5:161309645 | NC_000005.9 | c.641 G > A | p.(R214H) | De novo | SNV | Yes | 0 | Likely pathogenic (II) | PS2, PM2, PP2, PP3, PP5 | In-house | Pathogenic | SCV001160787 |
| 52 | Adult | F | SMC1A | chrX:53421723 | NC_000023.10 | c.2882 A > G | p.(Y961C) | De novo | SNV | No | 0 | Likely pathogenic (II) | PS2, PM2, PP2, PP3 | In-house | Probably pathogenic | SCV001160788 |
| 55 | Adult | M | TSC1 | chr9:135778027 | NC_000009.11 | c.2353 C > T | p.(R786*) | De novo | Stopgain | Yes | 0 | Pathogenic (Ia) | PVS1, PS2, PM2, PP5 | In-house | Pathogenic | VCV000048943.3 |
| 57 & 75 | Adult | M | FGFR3 | chr4:1803571 | NC_000004.11 | c.749 C > G | p.(P250R) | Father | SNV | Yes | 4.23E-06 | Likely pathogenic (III) | PS3, PP2, PP3 | In-house | Pathogenic | VCV000016340.6 |
| 58 | Pead | M | STXBP1 | chr9:130438189 | NC_000009.11 | c.1217 G > A | p.(R406H) | De novo | SNV | No | 0 | Likely pathogenic (I) | PS2, PM2, PP2, PP3, PP5 | Sapientia | Pathogenic | SCV001160791 |
| 59 | Pead | F | CNV (ATP2A1,TUFM) | chr16:28837450–29042118 | NC_000016.9 | 16p11.2 (205Kb) | Unknown | Deletion | No | Unknown | Pathogenic | No clear criteria | array-CGH | Pathogenic | SCV001160792 | |
| 61 | Adult | M | NONO | chrX:70518575 | NC_000023.10 | c.1190_1191del | p.(N397fs) | Mother | SNV | No | 0 | Likely pathogenic (I) | PVS1, PM2 | in-house | Probably pathogenic | SCV001160793 |
| 68 | Pead | M | ALG13 | chrX:110928268 | NC_000023.10 | c.320 A > G | p.(N107S) | De novo | SNV | No | 0 | Pathogenic (II) | PS1, PS2, PM2, PP3 | in-house | Likely pathogenic | SCV001160794 |
| 71 | Pead | F | CHD2 | chr15:93486194 | NC_000015.9 | c.948 C > A | p.(Y316*) | De novo | Stopgain | No | 0 | Pathogenic (Ia) | PVS1, PS2, PM2 | in-house | Pathogenic | SCV001160795 |
| 73 | Pead | M | NEDD4L | chr18:56037688 | NC_000018.9 | c.1822A > G | p.(M608V) | De novo | SNV | No | 1.15E-04 | Likely pathogenic (II) | PS2, PM2, PP2, PP3 | in-house | Pathogenic | SCV001160796 |
| 83 | Adult | M | PAFAH1B1 | chr17:2579865 | NC_000017.10 | c.967 T > A | p.(W323R) | De novo | SNV | No | 0 | Likely pathogenic (II) | PS2, PM2, PP2, PP3 | in-house | Pathogenic | SCV001160797 |
| 84 | Pead | M | CNV (RORA) | chr15:61328907–61398869 | NC_000015.9 | 15q22.2 | Unknown | Deletion | No | Unknown | Likely pathogenic | No clear criteria | array-CGH | Awaiting confirmation | SCV001160798 | |
| 88 | Pead | M | PPP3CA | chr4:101953424 | NC_000004.11 | c.1339 G > T | p.(A447S) | De novo | SNV | No | 0 | Likely pathogenic (II) | PS2, PM2, PP2, PP3 | in-house | Pathogenic | SCV001160799 |
| 89 | Pead | F | GRIN2A | chr16:9934843 | NC_000016.9 | c.1447 G > A | p.(G483R) | De novo | Stopgain | No | 0 | Pathogenic (Ia) | PVS1, PS2, PM2 | in-house | Pathogenic | SCV001160800 |
| 96 | Adult | F | SCN1A | chr2:166859242 | NC_000002.11 | c.4024 G > T | p.(G1342*) | De novo | Stopgain | No | 0 | Pathogenic (Ia) | PVS1, PS2, PM2, PP3 | in-house | Pathogenic | SCV001160801 |
| 97 & 98 | Adult | F | ANKRD11 | chr16:89341364 | NC_000016.9 | c.7571 A > G | p.(E2524G) | De novo | SNV | No | 0 | Pathogenic (IIIb) | PS2, PM1, PM2, PP2, PP3 | Sapientia | Pathogenic | SCV001160802 |
| 100 | Adult | M | KPTN | chr19:47984017 | NC_000019.9 | c.598_599insTA | p.(S200fs) | Biparental (Recessive) | FS Insertion | No | 0.0001 | Pathogenic (Ic) | PVS1, PM3, PP3 | in-house | Pathogenic | SCV001160803 |
| 101 | Adult | M | CACNA1A | chr19:13418964 | NC_000019.9 | c.1883C > T | p.(A628V) | De novo | SNV | No | 0 | Likely pathogenic (II) | PS2, PM2, PP2, PP3 | in-house | Pathogenic | SCV001160804 |
| 108 | Pead | F | SYNGAP1 | chr6:33409451 | NC_000006.11 | c.2209 C > T | p.(Q737*) | De novo | Stopgain | No | 0 | Pathogenic (Ic) | PVS1, PM2, PP2 | in-house | Pathogenic | SCV001160805 |
| 109 | Adult | F | SCN1A | chr2:166850722 | NC_000002.11 | c.4753 C > T | p.(R1585C) | De novo | SNV | No | 0.0001 | Likely pathogenic (III) | PS2, PP2, PP3 | in-house | Pathogenic | SCV001160806 |
| 111 | Adult | M | PTEN | chr10:89720852 | NC_000010.10 | c.1522 C > T | p.(R508*) | De novo | Stopgain | No | 0 | Pathogenic (Ia) | PVS1, PS2, PM2 | in-house | Pathogenic | SCV001160807 |
| Potential incidental findings: | ||||||||||||||||
| 6 | Adult | M | KCNH2 | chr7:150647388 | NC_000007.13 | c.2266 A > G | p.(M756V) | Mother | SNV | Yes | 0 | Likely Pathogenic (II) | PS3, PM2, PP2,PP3,PP5 | in-house | Unknown Significance | SCV001160808 |
| 65 | Adult | F | KCNQ1 | chr11:2790111 | NC_000011.9 | c.1171 C > T | p.(R391*) | De novo | Stopgain | Yes | 0.0001 | Pathogenic (Ia) | PVS1, PS2, PP5 | in-house | Pathogenic | SCV001160809 |
| 96 | Adult | F | MYH11 | chr16:15814100 | NC_000016.9 | c.4882 A > C | p.(K1628Q) | Father | SNV | Yes | 8.94E-05 | VUS | PP2, PP3, PP5 | in-house | Unknown Significance | SCV001160810 |
| 108 | Pead | F | VHL | chr3:10188233 | NC_000003.11 | c.376 G > A | p.(D126N) | Mother | SNV | Yes | 0.0001 | VUS | PP3, PP5 | in-house | Unknown Significance | SCV001160811 |
| Less secure (not ACMG confirmed), noteworthy variants: | ||||||||||||||||
| 29 | Adult | F | LRP2 | chr2:170055328 & chr2:170063464 | NC_000002.11 | c.[8546 G > C];[6766 G > T] | p.(G2849A);p.(D2256Y) | Comp Het | SNV | No | 0 / 0.0002 | VUS / VUS | PM2, PP3 & PM2, PP3 | in-house | Unknown Significance | SCV001160812 and SCV001160813 |
| 36 | Adult | M | OPHN1 | chrX:67339108 | NC_000023.10 | c.1343 C > T | p.(S448F) | Mother | SNV | No | 0 | VUS | PM2, PM3, PP3 | in-house | Unknown Significance | SCV001160814 |
FS deletion frameshift deletion, SNV single nucleotide variant, Comp Het compound heterozygote, VUS variant of unknown significance, inhouse in-house bioinformatics pipeline (GATK based), Sapientia Sapientia v1.9 pipeline.