Rare variant analysis of 4241 pulmonary arterial hypertension cases from an international consortium implicates FBLN2, PDGFD, and rare de novo variants in PAH

Table 2 Rare predicted deleterious FBLN2 and PDGFD variants* among 4175 PAH cases**

Case ID	Sex	Age_dx	PAH subclass	Ancestry	Gene ***	Exon	Nucleotide change	Amino acid change	Variant type	MAF (gnomAD exomes)	CADD score	Revel
08-018	F	70	IPAH	EUR	FBLN2	12	c.2639G>T	p.(Gly880Val)	D-Mis	1.63E−05	27.1	0.94
17-035	F	41	APAH	EAS	FBLN2	12	c.2666G>A	p.(Gly889Asp)	D-Mis	–	27.6	0.94
12-207	F	44	IPAH	EUR	FBLN2	13	c.2794T>C	p.(Phe923Leu)	D-Mis	2.11E−05	29.6	0.92
23-001	M	66	IPAH	EUR	FBLN2	14	c.2944G>T	p.(Asp982Tyr)	D-Mis	1.88E−05	34.0	0.95
29-031	F	57	IPAH	EUR	FBLN2	14	c.2944G>T	p.(Asp982Tyr)	D-Mis	1.88E−05	34.0	0.95
34-005	M	69	IPAH	EUR	FBLN2	14	c.2944G>T	p.(Asp982Tyr)	D-Mis	1.88E−05	34.0	0.95
W000210	F	52	IPAH	EUR	FBLN2	14	c.2944G>T	p.(Asp982Tyr)	D-Mis	1.88E−05	34.0	0.95
W000073	F	40	IPAH	AFR	PDGFD	2	c.166G>A	p.(Gly56Ser)	D-Mis	1.99E−05	22.9	0.64
JM950	F	2	IPAH	EUR	PDGFD	2	c.250C>T	p.(Arg84Trp)	D-Mis	1.59E−05	16.4	0.51
E012465	F	55	IPAH	EUR	PDGFD	3	c.385G>A	p.(Glu129Lys)	D-Mis	–	25.2	0.262
E014342	F	40	IPAH	EUR	PDGFD	3	c.385G>A	p.(Glu129Lys)	D-Mis	–	25.2	0.262
E014400	F	43	IPAH	EUR	PDGFD	3	c.442G>A	p.(Asp148Asn)	D-Mis	7.97E−06	25.2	0.41
E000844	F	39	IPAH	EUR	PDGFD	6	c.770T>C	p.(Leu257Pro)	D-Mis	4.01E−06	31.0	0.62
13-037	M	43	DTOX	EUR	PDGFD	6	c.883C>T	p.(Arg295Cys)	D-Mis	4.00E−06	35.0	0.56
23-025	F	41	IPAH	EUR	PDGFD	6	c.926C>G	p.Ser309Cys	D-Mis	–	28.4	0.22
E000820	F	73	IPAH	EUR	PDGFD	6	c.961T>A	p.(Tyr321Asn)	D-Mis	1.21E−05	33.0	0.34
E010173	F	74	IPAH	EUR	PDGFD	6	c.961T>A	p.(Tyr321Asn)	D-Mis	1.21E−05	33.0	0.34

*Rare, deleterious variants defined as gnomAD_exome_ALL AF ≤ 1.00E−04 and LGD or missense with variable REVEL cut-off (FBLN2 0.92 and PDGFD 0.22)
** Cases are heterozygous for the indicated variants
***Transcripts: FBLN2 NM_001998.3 and PDGFD NM_033135.4

ISSN: 1756-994X