Variant annotation and interpretation
The pathogenicity assessment and data interpretation rules of mutation
are based on the guidelines of the American College of Medical Genetics
and Genomics (ACMG) (Richards, et al., 2015). By querying 1000genomes,
ExAC and gnomAD, we excluded gene mutations whose frequency of the
population are more than 1% and removed non-functional mutation sites
(such as synonymous mutations, non-coding region mutations, etc.).We
performed gene function prediction (using software such as SIFT,
Polyphen2, CADD, etc.) and clinical symptoms comparison. At last, we
searched related disease databases and related references, and finally
found candidate gene mutation sites for family verification. The variant
annotation databases which were used include Human Genome hg19/GRCh37,
RefSeq, dbSNP, 1000 Genomes phase3, ExAC, and gnomAD and the
interpretation databases which were used include DGV, DECIPHER, OMIM,
UCSC, ClinVar, HGMD and PubMed.