Novel mutations in HSF4 cause congenital cataracts in Chinese families

BMC Medical Genetics

Table 2 Classification of HSF4 mutations in this study according to ACMG guideline

Family ID	Inheritance	Cataract Phenotype	Variation					PVS1	PM	PP			Classification
Family ID	Inheritance	Cataract Phenotype	gDNA change (hg19)	cDNA change	p.change	Status	type	PVS1	PM1	PM2	PP1	PP3
CAT-02	AD	Perinuclear	g.67199703G > C	c.314G > C	p.Ser105Thr	Hetero	missense		Y	Y	Y	Y	Likely pathogenic
CAT-12	AD	Total	g.67199519G > T	c.218G > T	p.Arg73Leu	Hetero	missense		Y	Y	Y	Y	Likely pathogenic
CAT-37	AD	Nuclear	g.67199622A > G	c.233A > G	p.Tyr78Cys	Hetero	missense		Y	Y	Y	Y	Likely pathogenic
CAT-50	AD	Total	g.67199621G > A	IVS5 c.233-1G > A	/	Hetero	canonical splice sites	Y	Y	Y	Y	Y	Pathogenic
CAT-51	AD	Total	g.67199488 T > C	c.187 T > C	p.Phe63Leu	Hetero	missense		Y	Y	Y	Y	Likely pathogenic

AD autosomal dominant, Hetero heterozygosity, Manually adjustments (italic) were performed for the PP3 criteria for all the mutations and all the criteria for c.233-1G > A
PVS1 = The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls;
PM1 = Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation;
PM2 = Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium;
PP1 = Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease;
PP3 = Multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.)

ISSN: 1471-2350