TABLE 1.

Positive molecular results and variants of unknown significance identified in the 150 fetuses of the cohort. *, positive reclassification; **, negative reclassification; ***, gene not involved in human disorder; #, fetus with a positive variant and variant of unknown significance.

Fetus	Gene	Variant segregation	Inheritance	Genomic position (hg19)	Protein
Positive variants in ES and CMA in parallel
1	ACTB	Paternal mosaicism	Autosomal dominant	chr7:g.5568935C>A	p. (Gly74Cys)
2	ANKRD11	De novo	Autosomal dominant	chr16:g.89349019G>A	p. (Arg1311*)
3	COL4A1	De novo	Autosomal dominant	chr13:g.110827050C>A	p. (Gly1082Val)
4	COL4A1	De novo	Autosomal dominant	chr13:g.110804766C>T	p. (Glu1615Lys)
5	DLL1	De novo	Autosomal dominant	chr6:g.170598799delG	p. (Pro51Hisfs*72)
6	EYA1	Maternally inherited	Autosomal dominant	chr8:g.72211426G>A	p. (Gln228*)
7	FGFR3	De novo	Autosomal dominant	chr4:g.1806119G>A	p. (Gly380Arg)
8	FLT4	De novo	Autosomal dominant	chr5:g.180040110C>T	p. (Gly1111Glu)
9	GRIN2B	De novo	Autosomal dominant	chr12:g.13717487_13717488del	p. (His895Leufs*15)
10	GUSB	Maternally inherited	Autosomal recessive	chr7:g.65439612C>T	p. (Arg382His)
		Paternally inherited		chr7:g.65444769G>A	p. (Leu176Phe)
11	HRAS	De novo	Autosomal dominant	chr11:g.534,287_534288delinsAA	p. (Gly12Val)
12	IGF1R	Maternally inherited	Autosomal dominant	chr15:g.99459270_99459271dup	p. (Pro637Cysfs*6)
13	L1CAM	Maternally inherited	X-linked recessive	chrX:g.153135930G>A	p. (Pro240Leu)
14	MRPS22	Paternally inherited	Autosomal recessive	chr3:g.139067142_139067143ins	p. (Ile161Asnfs*4)
		Maternally inherited		chr3:g.139069025G>A	p. (Arg170His)
15	NHS	Maternally inherited	X-linked dominant	chrX:g. [17393987C>G; 17393989del]	p. [(Pro36Arg); (Leu38Cysfs*158)]
16	NIPBL	De novo	Autosomal dominant	chr5:g.37057351C>T	p. (Gln2443*)
17	PTPN11	De novo	Autosomal dominant	chr12:g.112915523A>G	p. (Asn308Asp)
18	SLC26A2	Paternally and maternally inherited	Autosomal recessive	chr5:g.149359991C>T	p. (Arg279Trp)
19	SMO	Maternally inherited	Autosomal recessive	chr7:g.128845457T>C	p. (Phe252Leu)
		Paternally inherited		chr7:g.128846362C>T	p. (Arg400Cys)
20	TBX3	Paternally inherited	Autosomal dominant	chr12:g.115112386_115112393dup	p. (Glu452Glyfs*183)
21	TSEN54	Maternally inherited	Autosomal recessive	chr17:g.73518081G>T	p. (Ala307Ser)
		Paternally inherited		chr17:g.73518112delC	p. (Pro318Glnfs*24)
22	GREB1L	Maternally inherited	Autosomal dominant	chr18:g.19053061G>	p. (Arg751His)
22	Del 17q12	Maternally inherited	Autosomal dominant	17q12 (34842542–36104877)x1	ND
23	CREBBP	De novo	Autosomal dominant	chr16:g.3843495G>A	p. (Arg370*)
24	TUBB	De novo	Autosomal dominant	chr6:g.30691800A>G	p. (Met321Val)
25	PTPN11	De novo	Autosomal dominant	chr12:g.112910835A>G	p. (Ile282Val)
26	NFIA	De novo	Autosomal dominant	chr1:g.61554154C>T	p. (Arg121Cys)
27	ZNF148	De novo	Autosomal dominant	chr3:g.124951946G>A	p. (Gln542*)
28	del16p13.3	De novo	Autosomal dominant	16p13.3 (3767420–3860782)x1	ND
29	del17q25.3	De novo	Autosomal dominant	17q25.3 (79539041–81052322)x1	ND
30	del22q11.21	De novo	Autosomal dominant	22q11.2 (18893886–21386103)x1	ND
31	dup15q11.2	De novo	Autosomal dominant	15q11.2 (22833523–25223593)x3	ND
32	Trisomy 14	De novo—somatic mosaicism	Autosomal dominant	ND	ND
33	Trisomy 17	De novo—somatic mosaicism	Autosomal dominant	ND	ND
34	Trisomy 18	De novo	Autosomal dominant	ND	ND
35	Tetrasomy 12p	De novo	Somatic mosaicism	12p11.1-p12.33 (176047–34179852)x4	ND
Positive variants in ES after normal CMA
1	ASCC1#	Paternally and maternally inherited	Autosomal recessive	chr10:g.73970545dup	p. (Glu53Glyfs*19)
2	ASXL1	De novo	Autosomal dominant	chr20:g.31022449dup	p. (Gly646Trpfs*12)
3	BRAF	De novo	Autosomal dominant	chr7:g.140501302T>C	p. (Gln257Arg)
4	COL1A2	Maternally inherited	Autosomal dominant	chr7:g.94053703G>C	p. (Gly874Ala)
5	DYNC2H1	Paternally inherited	Autosomal recessive	chr11:g.103091449A>G	p. (Asp3015Gly)
		Maternally inherited		chr11:g.103124080del	p. (Leu3370Cysfs*35)
6	GNB2	De novo	Autosomal dominant	chr7:g.100275036A>G	p. (Lys89Glu)
7	KAT6B	De novo	Autosomal dominant	chr10:g.76789043_76789052del	p. (Ser1487Argfs*59)
8	KMT2D	De novo	Autosomal dominant	chr12:g.49445823delG	p. (Pro548Hisfs*382)
9	KMT2D	De novo	Autosomal dominant	chr12:g.49428657dup	p. (Leu3432Phefs*36)
10	LINS1	Maternally inherited	Autosomal recessive	chr15:g.101115226delT	p. (Glu200Lysfs*14)
		Paternally inherited		chr15:g.101115265_101115266del	p. (Lys186Serfs*17)
11	MTOR	De novo	Autosomal dominant	chr1:g.11189846A>C	p. (Phe1888Cys)
12	NRAS	De novo	Autosomal dominant	chr1:g.115258748C>G	p. (Gly12Arg)
13	PGM1	Paternally inherited	Autosomal recessive	NM_002633.2: c.423delA	p. (Ala142Glnfs*2)
		Maternally inherited		NM_002633.2:c.157_158delinsG	p. (Gln53Glyfs*15)
14	PPM1D	De novo	Autosomal dominant	chr17:g.58740467C>T	p. (Arg458*)
15	SOS1	De novo	Autosomal dominant	chr2:g.39250269C>T	p. (Gly434Arg)
16	SOS1	De novo	Autosomal dominant	chr2:g.39249914G>A	p. (Arg552Lys)
17	SCYL2	Paternally inherited	Autosomal recessive	chr12:g.100676845delG	p. (Asp33Metfs*13)
		Maternally inherited		chr12:g.100676924dup	p. (Glu60Glyfs*8)
Variants of unknown significance in ES and CMA in parallel
1	NUP188*	Maternally inherited	Autosomal recessive	chr9:g.131760903G>A	p.?
		Paternally inherited		chr9:g.131745626_131745627delinsG	p. (Cys617Trpfs*2)
2	EFEMP2*	Paternally and maternally inherited	Autosomal recessive	chr11:g.65638118A>G	p. (Cys127Arg)
	RAG1	Paternally and maternally inherited	Autosomal recessive	chr11:g.36596621C>G	p. (Tyr589*)
3	CUX1	Maternally inherited	Autosomal dominant	chr7:g.101921327C>A	p. (Tyr541*)
4	DLL1	Maternally inherited	Autosomal dominant	chr6:g.170597444C>A	p. (Gly185*)
5	DNAH11	Maternally inherited	Autosomal recessive	chr7:g.21627820G>T	p.?
		Paternally inherited		chr7:g.21856224G>A	p. (Arg3491His)
6	GREB1L	Maternally inherited	Autosomal dominant	chr18:g.19019482A>T	p. (Asp278Val)
7	del1q21.1	ND	Autosomal dominant	1q21.1 (145414780–145826931)x1	ND
8	del6p21.32 (BRD2***)	De novo	Autosomal dominant	6p21.32 (32940674–32947911)x1	ND
Variants of unknown significance in ES after normal CMA
1	CSPP1#	Paternally and maternally inherited	Autosomal recessive	chr8:g.67986545_67986546del	p. (Lys56Serfs*6)
2	FGF8*	Paternally inherited	Autosomal dominant	chr10:g.103530204C>T	p. (Arg195Gln)
3	MYCN*	De novo	Autosomal dominant	chr2:g.16082365C>T	p. (Pro60Leu)
4	dupXq28 (IDS**)	Maternally inherited	X-linked recessive	Xq28 (148564275–148798438)x3	ND
5	KAT7***	De novo	Autosomal dominant	chr17:g.47900657A>G	p.Ser494Gly
6	KMT2E	Maternally inherited	Autosomal dominant	chr7:g.104753422del	p. (His1740Profs*132)
7	LZTR1	De novo	Autosomal dominant	chr22:g.21342341A>G	p. (Asn148Ser)
	dup1q21.1-1q21.2	De novo	Autosomal dominant	1q21.1q21.2 (146397357–148344744)x3	ND