Table 1 Genes carrying sequence variants displaying significant deficit of homozygosity

From: Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality

		Homozygote count: by dataset			Homozygote count: combined			Gene: functional annotation			Significant single variants: functional annotation^a
Gene	Test^b	Datasets	O	E	O	E	O/E	OMIM ID (inheritance)	KO mouse	Human cell-line	Pos (Hg38)^c	Ref/Alt	Consequence (HGVS)	ClinVar (N)
Loss-of-function variants
DHCR7	G,V	I/D/N/S/U/F	0/0/0/0/0/0	31/11/3.5/0.74/53/0.82	0	100	0	270400 (AR^c)	Lethal	Non-Essential	chr11:71,435,840	C/G	Splice acceptor c.964-1 G > C	LP(2),P(27)
TSFM	G,V	I/D/N/S/U/F	0/1/0/0/0/0	3e-5/0.11/0.04/0.088/0.044/29	1	29.2	0.034	610505 (AR^c)	Lethal	Essential	chr12:57,796,461	C/T	Stop gained p.Gln307Ter	B(1),LP(1),P(4)
CCDC59	G,V	I/D/N/S/U/F	0/0/0/0/0/0	4/6.7/4.6/0.73/4.5/1.2	0	21.6	0		Lethal E9.5	Essential	chr12:82,354,490	CTTAC../C	Splice donor c.561_564+4del
ATP5PB	G,V	I/N	0/0	16/0.00064	0	15.8	0		Lethal	Essential	chr1:111,459,496	C/T	Stop gained p.Arg185Ter
MTG2	G,V	I/D/N/S/U/F	0/0/0/0/0/0	0.3/0.77/0.16/0.49/0.82/11	0	13.4	0		Lethal E9.5	Essential	chr20:62,198,729	AG/A	Frameshift p.Gly191AlafsTer14
BRF2	G,V	I/N/S/U	0/0/0/0	11/0.0075/0.00041/0.019	0	11.1	0			Essential	chr8:37,848,595	C/T	Splice donor c.214+1 G > A
GTF2H3	G,V	I/D/N/S/U/F	0/0/0/0/0/0	1.7/4.4/0.9/1.4/1.9/0.4	0	10.7	0			Essential	chr12:123,633,862	G/A	Start lost p.Met1?
CENPF	G	I/D/N/S/U	0/0/0/0/0	9.1/0.0071/0.34/0.096/1	0	10.5	0	243605 (AR^c)	Viable	Non-Essential
PUM3	G,V	I/D/N/S/U	0/0/0/0/0	8.1/0.44/0.047/0.018/1.7	0	10.2	0			Non-Essential	chr9:2,837,222	ATT/A	Frameshift p.Lys87IlefsTer12
ELOF1	G,V	I/N/S/U	0/0/0/0	10/0.064/0.0059/0.00076	0	10.2	0		Lethal E12.5	Non-Essential	chr19:11,554,278	AC/A	Frameshift p.Gln23HisfsTer15
PKHD1	G,V	I/D/N/S/U/F	0/0/0/0/0/0	4/0.07/0.0036/0.0015/0.49/5.1	0	9.62	0	263200 (AR^c)	Sub-Viable	Non-Essential	chr6:52,058,349	G/A	Stop gained p.Arg496Ter	LP(1),P(10)
RPAP2	G,V	I/D/N/S/U	0/0/0/0/0	9.1/0.0052/0.0091/0.0013/0.11	0	9.26	0			Essential	chr1:92,333,464	TGAGT../T	Frameshift p.Lys512ValfsTer20
WARS2	G,V	I/U	0/0	9.1/0.0081	0	9.10	0	617710 (AR)	Lethal E9.5	Essential	chr1:119,033,158	TG/T	Frameshift p.His279MetfsTer4
PNKP	G,V	I/D/N/S/U	0/0/0/0/0	2.5/2.3/1.2/0.13/2.4	0	8.53	0	613402 (AR),616267 (AR)	Lethal	Essential	chr19:49,862,369	A/G	Splice donor c.1029+2 T > C	LP(2),P(2)
BRIP1	G	I/D/N/S/U	0/0/0/0/0	7.5/0.0056/0.043/0.00026/0.21	0	7.74	0	114480 (AD),609054 (AR)	Viable	Essential
GBE1	G,V	I/D/N/S/U	0/0/0/0/0	1.8/2.2/2/0.33/1	0	7.29	0	232500 (AR^c)	Lethal	Non-Essential	chr3:81,648,854	A/G	Splice donor c.691+2 T > C	P(11)
AGK	G,V	I/D/U	0/0/0	5.8/0.00055/0.042	0	5.79	0	212350 (AR^c)	Sub-Viable	Non-Essential	chr7:141,649,323	A/ATAAC	Frameshift p.Ile348AsnfsTer38
CDC7	G,V	I/U	0/0	5.3/0.0045	0	5.34	0		Lethal E9.5	Essential	chr1:91,520,185	T/G	Stop gained p.Tyr412Ter
DIAPH3	G	I/D/N/S/U	0/0/0/0/0	1.3/1.2/2.3/0.058/0.44	0	5.29	0	609129 (AD)	Lethal	Non-Essential
Moderate impact
MRPS30	V	I/D/N/S/U/F	0/1/0/0/0/0	2.8/7.6/7.5/1/4.9/24	1	48.2	0.021			Essential	chr5:44,811,105	T/G	Missense p.Ile233Arg
PMM2	V	I/D/N/S/U/F	0/0/2/0/2/0	5.2/15/6.3/1.6/15/11	4	54.1	0.074	212065 (AR)	Lethal E9.5	Non-Essential	chr16:8,811,153	G/A	Missense p.Arg141His	LP(2),P(29)
HYLS1	V	F	1	15	1	14.9	0.067	236680 (AR)	Lethal E15.5	Non-Essential	chr11:125,900,000	A/G	Missense p.Asp211Gly	P(6)
MVD	V	I/D/N/S/U	0/0/0/0/0	0.85/2/0.58/0.34/7.3	0	11.1	0	614714 (AR)	Lethal E9.5	Essential	chr16:88,663,006	C/T	Splice region c.70+5 G > A
GLE1	V	I	0	11	0	11.0	0	253310 (AR),611890 (AR)	Lethal	Essential	chr9:128,536,414	G/A	Missense p.Arg569His	LP(2),P(2)
CASP9	V	I/D/N/S/U/F	0/0/0/0/0/1	1.2/3.9/1.6/0.72/2.3/2.2	1	11.9	0.084		Lethal	Non-Essential	chr1:15,506,000	T/G	Missense p.His237Pro
Total	—	—	—	—	8	452	—	—	—	—	—	—	—	—

Loss-of-function variants: stop-gained, frameshift, essential splice donor and acceptor sequence variants; Moderate impact: missense, inframe indel, splice region sequence variants; Ref/Alt: reference and alternative alleles, alleles sequences over five base pairs are depicted as “..”; Consequence (HGVS): calculated variant consequence using VEP and sequence variant description according to HGVS nomenclature; E: number of homozygotes expected under HWE, O: number of homozygotes observed; DATASETS: I = Iceland, D = Denmark, N = Norway, S = Sweden, U = UK Biobank, F = Finland (Finngen R5); ClinVar (N): Clinical significance of reported as pathogenic in ClinVar and N is the number of submitted records in parenthesis, P = pathogenic, LP = likely pathogenic.; OMIM ID (Inheritance): OMIM ID of mendelian disease linked to gene, early lethality is indicated with a footnote. The mode of inheritance is indicated in parenthesis.; KO mouse: Homozygous knockout mouse mortality phenotypes (MGI and IMPC). Lethal = complete embryonic lethality, Sub-Viable = incomplete penetrance of embryonic lethality, Viable = KO mouse viable, empty = Human gene ortholog not targeted in mouse (see Supplementary Data 1 for details); Human cell-line: Genes essential for cell growth in human cell lines (DepMap). Essential = essential for cell growth in human cell-lines, Non-Essential = Non-essential for cell growth in human cell-lines. (see Supplementary Data 4 and 6 for details).
^aAnnotation is shown for variants that are significant on a single-variant test, see Supplementary Data 4.
^bSignificant homozygous deficit: G = gene-based test, V = single-variant test.
^cEarly lethality reported (see Supplementary Data 4).

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Table 1 Genes carrying sequence variants displaying significant deficit of homozygosity

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