Table 3.

Details of Rare Variants Identified Through Filtering of Candidate Genes With Frequency <0.005

Gene	Variant	Exonic function	Transcript/cDNA/protein information	dbSNP150	gnomAD WES ALL	gnomAD WES SAS	gnomAD WES EAS	SIFT score	PolyPhen2 HVAR score	CADD	GERP++	1‐b	2‐a	2‐b
PLOD2	chr3:145799628T>A	Nonsynonymous SNV	NM_182943/c.A1255T/p.Thr419Ser	rs776654051	3.99E−06	0	5.44E−05	0.88 (T)	0.515 (P)	10.78	5.53	0/1	0/0	0/0
TMEM25	chr11:118402939G>A	Nonsynonymous SNV	NM_032780/c.G145A/p.Ala49Thr	rs782188288	1.00E−04	1.00E−04	0.0013	0.55 (T)	0.209 (B)	15.48	3.26	0/0	0/1	0/1

Chromosome positions are given for build GRCh37. Both variants are not present in the gnomAD WGS and the 1000 Genome databases. SIFT score and prediction: 0–0.05 damaging (D); >0.05 tolerated (T). PolyPhen2 HVAR score and prediction: 0–0.446 benign (B); 0.446–0.908 possibly damaging (P); 0.908–1.0 probably damaging (D).

CADD = Combined Annotation Dependent Depletion tool, higher values indicate a higher chance of being damaging (max 60); GERP++ = Conservation score based on the likelihood of substitutions and the deviation thereof, higher score indicates more conservation at the site (maximum 6); HVAR = Polyphen scores trained on HumVar data meant for Mendeliandiseases (Adzhubei et al. Nat Methods 2010); WES ALL = exome data of all populations; WES EAS = exome data of East Asian population; WES SAS = exome data of South Asian population; SNV = single nucleotide variant.