2.7 Gene variants interpretation
Based on the ACMG guidelines, the pathogenicity of the variation was
classified into five subtypes, including pathogenic, likely pathogenic,
unknown, likely benign, and benign. Then the disease risk of the
examined neonates was graded to three-level risks (high risk, moderate
risk, and low risk) and carrier, according to the pathogenicity of the
variation and the genetic inheritance pattern (Supplementary Figure 2).
Each grade is defined as follows:
High risk : A pathogenic or likely pathogenic
variant of the genes that are
autosomal dominant or Y-linked; Two pathogenic or likely pathogenic
variants of the genes that are autosomal recessive; Female newborns
carry two pathogenic or likely pathogenic variants of X-linked dominant
genes; Male newborns carry a pathogenic or likely pathogenic variant of
X-linked recessive genes.
Moderate risk : A pathogenic or likely pathogenic variant, and a
potent variant of unknown significance of the genes that are autosomal
recessive; Female newborns carry a pathogenic or likely pathogenic
variant, and a potent unknown significance variant of X-linked recessive
genes.
Low risk : A pathogenic, likely pathogenic, or unknown
significance variant, and a nonvirulent variant with unknown meaning of
the genes that are autosomal recessive; A unknown significance variant
of the genes that are autosomal dominant or Y-linked; Female newborns
carry a pathogenic, likely pathogenic, or unknown significance variant
and a nonvirulent variant with unknown meaning of X-linked recessive
genes.
Carrier : A pathogenic or potentially pathogenic variation of
autosomal recessive genes; Female newborns carry a pathogenic or likely
pathogenic variant of X-linked recessive genes.