Table 2.
Clinical relevant changes in variant classification after re-evaluation.
| Family | Affected | Gene | Variant | Inheritance mode | Gene classification | Variant classification | Explains phenotype | Phenotype |
|---|---|---|---|---|---|---|---|---|
| MR205 | 3, m | DARS2 | c.228-12 C > G, p.? | AR | established (11 affected from 8 families, 2 publications) | B (BS1,BS2) | no | moderate ID, seizures, cerebral palsy, cerebral atrophy |
| MR154 | 2, m | FOXRED1 | c.874 G > A, p.(Gly292Arg) | AR | established (8 affected from 7 families, >3 publications, functional analysis) | VUS (PM2,PM3,PP3) | no | moderate ID, seizures, muscular hypotonia |
| MR-SYR-04 | 2, f | HACE1 | c.402+5 G > A, p.? | AR | established ( >14 affected from >6 families, >2 publications) | VUS (PM2,PM3_Supporting,PP3) | no | severe ID, ataxia, muscular hypotonia, recurrent infections |
| MR319 | 2, f | MTHFR | c.199 C > T, p.(Pro67Ser) | AR | established ( >20 affected from >20 families, >2 publications) | VUS (PM2,PM3_Supporting,PP3) | no | severe ID, microcephaly, abnormality of the optic nerve, EEG abnormalities, cerebral atrophy, leukodystrophy |
| MR081 | 2, m | TRMT10A | c.348 G > C, p.(Lys116Asn) | AR | established ( >6 affected from >3 families, >3 publications) | VUS (PM2,PM3_Supporting) | no | severe ID, microcephaly, short stature, behavioral abnormality, cerebral calcification |
| MR326 | 2, fm | LINS1 | c.786_842del, p.(Arg263_Ser281del) | AR | established ( >7 affected from >3 families, >2 publications) | VUS (PM2,PM3_Supporting,PM4) | no | moderate ID, aggressive behavior, stereotypical motor behaviors, strabismus |
| MR-ER-31711 | 1, m | UBE3B | c.[1445 T > A;1616T > C], p.[(Leu539Pro;Leu482His)] | AR | established ( >9 affected from >7 families, >2 publications) | VUS (PM2,PM3,PP3) | no | severe ID, feeding problems in infancy, abnormalities of the face, submucous cleft palate, strabismus, deafness, hypoplastic corpus callosum, hydrocephalus |
| MR058 | 1, m | SLC6A8 | c.644 A > G, p.(Glu215 Gly) | XL | established ( >10 affected from >9 families, >3 publications) | VUS (PM2,PM3_Supporting,PP3) | no | moderate ID, feeding problems in infancy, congenital megacolon |
| MR-SYR-34 | 3, fm | ADGRG1 | c.64+5G > A, p.? | AR | established ( >12 affected from >12 families, >3 publications) | VUS (PM2,PM3_Supporting) | no | very severe ID, seizures, limb hypertonia, mental deterioration, deafness, cerebral atrophy |
| MR305 | 1, m | PIGA | c.1261 G > C, p.(Gly421Arg) | XL | established ( >14 affected from >7 families, >3 publications) | VUS (PM2,PM3_Supporting,PP3) | no | very severe ID, seizures, microcephaly, spasticity, abnormalities of the face, gingival hypertrophy, nystagmus, scaphocephaly, schizencephaly, leukodystrophy, basal ganglia calcification |
| MR092 | 2, m | TSEN15 | c.346 C > T, p.(His116Tyr) | AR | published candidate (5 affected from 3 families, no functional analysis) | not applicable | not applicable | moderate ID, microcephaly |