Variants in genes related to development of the urinary system are associated with Mayer–Rokitansky–Küster–Hauser syndrome

Table 2 In silico analysis of sequence variants found by WES in MRKH patients

Case ID	Zygosity	Gene	Ref mRNA No	Mutation type	Variants	Amino acid change	GnomAD-EAS	PolyPhen2/SIFT/MutationTaster/LRT/FATHMM-MKL	ACMG
Fc-M-1	Hetero	TBC1D1	NM_015173	frameshift	c.2553delC	p.R854Efs*24	0	NA/NA/D/NA/NA	P: PVS1 + PM2 + PP3
Fc-M-2	Hetero	KMT2D	NM_003482	missense	c.2992C>G	p.P998A	0.0000557	B/D/N/N/D	VUS: BP4
Fc-M-2	Hetero	LIFR	NM_002310	missense	c.1418C>G	p.S473C	0	P/D/N/N/N	VUS: PM2 + BP4
Fc-M-3	Hetero	TBC1D1	NM_015173	missense	c.1069G>C	p.E357Q	0.0002	D/D/D/D/D	VUS: PM2 + PP3 + BP1
Fc-M-4	Hetero	HOXD3	NM_006898	missense	c.575C>G	p.P192R	0	D/D/D/D/D	VUS: PM2 + PP3
Fc-M-6	Hetero	DLG5	NM_004747	stop codon	c.418C>T	p.Q140*	0	NA/NA/D/N/D	P: PVS1 + PM2 + PP3
Fc-M-7	Hetero	KMT2D	NM_003482	missense	c.1754C>T	p.P585L	0	D/D/D/NA/D	VUS: PM2 + BP4
Fc-M-7	Hetero	CLIP1	NM_002956	missense	c.1498C>T	p.R500C	0	D/D/D/N/D	VUS: PM2 + PP3
Fc-M-8	Hetero	GLI3	NM_000168	missense	c.895C>G	p.L299V	0	P/D/D/D/D	VUS: PM2 + PP3 + BP1
Fc-M-9	Hetero	HIRA	NM_003325	missense	c.845A>G	p.K282R	0	B/T/D/D/D	VUS: PM2 + BP1
Fc-M-10	Hetero	GATA3	NM_002051	missense	c.1178C>T	p.P393L	0.00005631	B/D/D/D/D	VUS: PM2 + PP2 + PP3

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects. In this study, we referred to the allele frequencies in the East Asian (EAS) population
Pathogenicity items: Polyphen2: D, probably damaging; P, possibly damaging; B, benign. SIFT: D, damaging; T, tolerated. MutationTaster: D, disease causing; N, polymorphism. LRT: D, deleterious; N, neutral. FATHMM-MKL: D, damaging; N, neutral. NA, not applicable
ACMG item: ACMG, American College of Medical Genetics and Genomics guidelines; VUS, variant of uncertain significance; P, pathogenic variant; LB, likely benign variant

ISSN: 1479-7364