Table 2. Characteristics of 6 Patients With Variants in DIAPH1.

Proband ID	Ethnicity	Sex	Type	Class	Gene	Position (GRCh37)	AA change	Bravo WGS Freq a	gnomAD WES Freq	MetaSVM	CADD1.6
Yale Center for Mendelian Genomics (24 MMD cases)
KMM_2-1	European	Male	Transmitted from father	D-Mis	DIAPH1	5:140905715:C:T	p.R1155Q	8.0 × 10−6	2.4 × 10−5	T	27.8
KMM_39-1	European	Male	DNV	Splicing	DIAPH1	5:140962861:T:C	c.534-2A>G	NA	NA	NA	33
KMM_42-1	European	Female	DNV	D-Mis	DIAPH1	5:140961905:A:G	p.C220R	NA	NA	D	28.2
University of Texas Health Science Center at Houston (84 MMD cases)
MM 087	African American/African	Female	Unphased	D-Mis	DIAPH1	5:140908798:G:A	p.L907F	8.0 × 10−6	NA	T	23.9
MM 087	African American/African	Female	Unphased	D-Mis	DIAPH1	5:140908799:C:A	p.M906I	8.0 × 10−6	NA	T	22.6
MM 094	European	Male	Transmitted from father	D-Mis	DIAPH1	5:140955835:C:T	p.E475K	4.5 × 10−4	1.3 × 10−3	T	28.8
MM 117	African American/African	Female	Unphased	T-Mis	DIAPH1	5:140954569:C:A	p.D536Y	8.0 × 10−6	4.1 × 10−6	T	15.99

Abbreviations: AA, amino acid; Bravo WGS Freq, Bravo whole-genome sequencing frequency; CADD1.6, combined annotated-dependent depletion; D-Mis, deleteriousness of missense variants; DNV, de novo variant; gnomAD WES Freq, Gnome aggregation database whole exome sequence frequency; MetaSVM, meta-analytic support vector machine; MMD, moyamoya disease; NA, not applicable.

^a This global frequency is based on 132 345 genomes in the Bravo database and is independent of ethnicity; Gnome Aggregation Database Whole Exome Sequence Frequency. This frequency is based on 125 748 exomes in the gnomAD database (v2.1.1) and is independent of ethnicity. Meta-analytic support vector machine is an ensemble score that predicts the tolerability of a variant. Combined annotated-dependent depletion is a validated tool for scoring the deleteriousness of single nucleotide deletions, insertions, or variations.