Table 2.
Genes carrying sequence variants for which there is currently insufficient evidence to support a phenotypic expansion involving CDH/DE
| Gene | Disorder (MIM number) | Subject ID; variant; ACMG interpretation | Homolog expressed in the developing mouse diaphragm?† | CDH Pathogenicity Score‡ | Other cases of CDH/DE reported for this gene/disorder in humans |
|---|---|---|---|---|---|
| CDK13 § | Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (MIM: 617360) | Subject 1; c.2524A>G [NM_003718.5], p.(Asn842Asp); Pathogenic | Yes | 75% | No/No |
| CHAMP1 | Mental retardation, autosomal dominant 40 (MIM: 616579) | Subject 2; c.1741delG [NM_001164144.3], p.(Glu581Asnfs*4); Pathogenic | Yes | 81% | No/No |
| CHD8 | Autism, susceptibility to, 18 (MIM: 615032); CHD8-related intellectual disability and overgrowth | Subject 4; c.6394A>C [NM_001170629.2], p.(Asn2132His); VUS | Yes | 52% | No/No |
| PIGL | CHIME syndrome (MIM: 280000) | Subject 6 ; c.[500T>C];[660+1G>T] [NM_004278.4], p.[(Leu167Pro)];[(?)], SpliceAI: ΔS donor loss; Pathogenic/Likely Pathogenic | Yes | 82% | No/No |
| SACS | Spastic ataxia, Charlevoix-Saguernay type (MIM: 270550) | Subject 8; c.[10298C>G];[c.3655C>T] [NM_014363.6], p.[(Pro1219Ser)];[(Thr3433Arg)]; VUS/Likely Benign | Yes | 86% | No/No |
| SETD5 ¶ | Mental retardation, autosomal dominant 23 (MIM: 615761) | Subject 9; c.2302C>T [NM_001080517.3], p.(Arg768*); Pathogenic | Yes | 38% | No/No |
| GNAI1 β | N/A (MIM: 139310) | Subject 9; c.134G>T [NM_002069.6], p.(Gly45Val); VUS | Yes | 93% | No/No |
| TBX3 | Ulnar-mammary syndrome (MIM: 181450) | Subject 12; c.337T>G [NM_005996], p.(Trp113Gly); Likely Pathogenic | Yes | 95% | No/No |
| TCF4 | Pitt-Hopkins syndrome (MIM: 610954) | Subject 13; c.1570C>T [NM_001083962.2], p.(Gln524*); Pathogenic | Yes | 93% | No/No |
Is the mouse orthologue expressed in the developing diaphragm at embryonic day (E)11.5, E12.5 and E16.5 based on whole-transcriptome expression profiles published by Russell et al. (Russell et al., 2012)? This pattern is not seen in ~ 20% of the genes evaluated by Russell et al.
A machine learning-generated centile score that ranks the similarity of this gene to a set of 31 known CDH gene in comparison to all RefSeq genes (Callaway et al., 2018).
The individual with the CDK13 variant was previously reported as Subject 12 by Hamilton et al. (Hamilton et al., 2018).
The individual with the SETD5 and GNAI1 variants was previously reported by Rawlins et al. (Rawlins et al., 2017). N/A = Not applicable