Table 2.
Clinical and Genetic Features of Individuals with Apparently Inherited, High Impact Variants in ANKRD11
| Proband ID | 265784 | 258544 | 276420 | 279343 | 301622 | 303467 | 305225 |
|---|---|---|---|---|---|---|---|
| NC_000016.9 Genomic Variant | g.89334964_89334970dup | g.89350555del | g.89350831del | g.89349780_89349781del | g.89351044_89351045del | g.89346281del | g.89348863G>A |
| NM_013275.5 cDNA | c.7909_7915dup | c.2397del | c.2119del | c.3170_3171del | c.1908_1909del | c.6670del | c.4087C>T |
| NP_037407.4 Protein | p.Leu2639GlnfsTer113 | p.Glu800LysfsTer63 | p.Glu707LysfsTer12 | p.Lys1057ArgfsTer10 | p.His636GlnfsTer26 | p.Glu2224ArgfsTer113 | p.Arg1363Ter |
| Inheritance | uncertain (subsequently confirmed de novo) | uncertain (subsequently confirmed de novo) | maternal | maternal | maternal | paternal | paternal |
| Child/parental VAF | 4/4:? | 9/5:? | 20/20:23/23 | 32/36:31/49 | 26/28:26/24 | 13/10:6/13 | 35/36:41/46 |
| Consequence | frameshift variant | frameshift variant | frameshift variant | frameshift variant | frameshift variant | frameshift variant | stop gained |
| Birth weight | −1.23 | −0.08 | −0.54 | −1.29 | −1.66 | 0.32 | 0.16 |
| Height | −2.39 | −1.87 | −0.76 | −2.92 | −2.06 | −2.37 | −4.02 |
| Weight | −2.49 | −0.5 | −0.41 | −3.58 | −1.45 | −0.52 | −2.97 |
| OFC | −2.38 | −0.74 | −2.48 | −4.78 | −3.35 | −2.83 | −2.64 |
| HPO terms (not used in similarity analysis) | Abnormal facial shape; Intellectual disability; mild; Microcephaly; Short stature | 2-3 toe syndactyly; Abnormal facial shape; Abnormality of dental morphology; Avascular necrosis of the capital femoral epiphysis; Broad finger; Clinodactyly of the 5th finger; Cryptorchidism; Global developmental delay; High palate; Short neck; Strabismus | Anteverted nares; Behavioral abnormality; Global developmental delay; Hirsutism; Hypermetropia; Protruding ear; Sensorineural hearing impairment; Short attention span; Synophrys; Wide mouth | Brachycephaly; Clinodactyly of the 5th finger; Conductive hearing impairment; Global developmental delay; Prominent metopic ridge; Short stature; Sparse scalp hair | Fetal fifth finger clinodactyly; Moderate global developmental delay; Short stature | Delayed speech and language development; Edema of the dorsum of feet; Feeding difficulties; Fine hair; Immunologic hypersensitivity; Infra-orbital crease; Moderate global developmental delay; Neonatal hypotonia; Short foot; Thin upper lip vermilion; Upslanted palpebral fissure | 2-3 toe syndactyly; Failure to thrive in infancy; Frontal bossing; Long eyelashes; Moderate global developmental delay; Sacral dimple; Short stature |
| Family history | none | none | father has intellectual disability (variant maternally inherited) | father has mild KBG on clinical reassessment | none | none | none |
| Clinically confirmed | yes | yes | yes | yes | possible | yes | yes |
| Notes | DNM in SOX10 not classified | referred with a clinical diagnosis of KBG | also has KMT6A in-frame dup (mat) amd TECTA nonsense mutation (pat) both unclassified | ACAN variant reported (likely benign) | missense in TRIP12 reported (likely benign) | TSC2 variant reported (unclassified) | no variants reported |
Abbreviations: VAF, variant allele frequency; DNM, de novo mutation; OFC, occipito-frontal circumference.