Whole-exome sequencing identifies new pathogenic germline variants in patients with colorectal polyposis

Table 1 Characterization and clinical-pathological assessment of participants of study

Gender	n (%)
Male	14 (48.1)
Female	13 (51.9)
Age of polyposis diagnosis	Mean (minimum-maximum)
	51 (19-69)
Polyposis type
Classic polyposis	2 (7.4)
Attenuated polyposis	25 (92.6)
Age of first diagnosed tumor	Mean (minimum-maximum)
	51 (19-64)
Primary diagnosed tumor site1
Colorectal	13 (76.4)
Endometrium	1 (5.9)
Breast	1 (5.9)
Prostate	1 (5.9)
Thyroid	1 (5.9)
Age of second diagnosed tumor	Mean (minimum-maximum)
	59 (49-69)
Second primary diagnosed tumor site
Colorectal	2 (11.8)
Breast	1 (5.9)
Thyroid	1 (5.9)
Status
Alive, in follow-up	26 (96.3)
Deceased	1 (3.7)

¹Total number of cancers affected patients is 17.

Table 2 Pathogenic and likely pathogenic variants identified in the participants of study

Index case	Polyposis/tumor (age at diagnosis)	Gene	Transcript	cDNA change	Protein change	Revel	GnomAD AF	Classification1
1165	Attenuated polyposis (53)/CRC (52)	PCSK7	NM_004716.3	c.1054+1del	-	NP	NR	P
1488	Attenuated polyposis (40)/endometrium hyperplasia (50)	DKK4	NM_014420.3	c.108del	p.(Lys37Argfs50)	NP	NR	LP
		NTHL1	NM_002528.7	c.244C>T	p.(Gln82)	NP	1.40e-03	P
		PIDD1	NM_145886.3	c.2042-2A>G	-	NP	8.41e-05	LP
1490	Attenuated polyposis (52)	ST7 L	NM_017744.5	c.540dup	p.(Tyr181Ilefs3)	NP	NR	LP
1536	Breast (58)/attenuated polyposis (63)	CD44	NM_001001392.2	c.250C>T	p.(Gln84)	NP	NR	LP
		TG	NM_003235.5	c.4588C>T	p.(Arg1530)	0.329	8.354e-05	LP
1831	Attenuated polyposis (36)	HLTF	NM_003071.3	c.1160+2T>C	-	NP	3.98E-06	P
		MUC16	NM_024690.2	c.14516del	p.(Gly4839Valfs55)	NP	8.032e-06	LP
2325	Attenuated polyposis (59)/CRC (59)	OBSCN	NM_001271223.2	c.3574C>T	p.(Gln119)	NP	NR	LP
2448	Attenuated polyposis (19)/CRC (19)	PMS2	NM_000535.7	c.1882C>T	p.(Arg628)	NP	1.59E-05	P
278	Attenuated polyposis (55)/CRC (55)	MUC16	NM_024690.2	c.14338_14341del	p.(Thr4780 Leufs4)	NP	1.21E-05	LP
		TINF2	NM_001099274.3	c.1202dup	p.(Asn401 Lysfs19)	NP	NR	LP
454	Classic polyposis (19)	FRK	NM_002031.3	c.190C>T	p.(Arg64)	NP	1.591e-05	LP
517	Attenuated polyposis (56)	PNKP	NM_007254.4	c.1541_1548dup	p.(Gln517Cysfs)	NP	NR	P
547	Attenuated polyposis (51)/CRC (51)	A1CF	NM_014576.4	c.826C>T	p.(Arg276)	NP	7.982e-06	LP
907	Attenuated polyposis (61)	AHRR	NM_001377236.1	c.938C>A	p.(Ser313)	NP	NR	LP

¹Classification according to American College of Medical Genetics and Genomics criteria[25].

AF: Allele frequency; NP: Not predicted; NR: Not reported; P: Pathogenic; LP: Likely pathogenic.