Identification of a de novo variant in BCAP31 by full
genome analysis
Since exome sequencing did not reveal candidate variants in the primary
screen, we performed Chromium (10x Genomics) Linked‐Reads whole genome
sequencing on the patient and her biological parents. All variants were
called and phased with Long Ranger BASIC and ALIGN Pipelines and
followed by filters of allelic frequency with threshold set at 0.01 for
missense, indels and splice site mutations. Then, the remaining variants
after filtering were evaluated according to three possible genetic
models: autosomal recessive, autosomal dominant and X-linked recessive.
As the parents were without the disorder, only de novo variants
were considered in the autosomal dominant and X-linked recessive models.
After determining that the sequence quality was high by expert
inspection, and literature review that showed good correlation with the
associated clinical phenotype, we identified a de novoheterozygous variant in the BCAP31 gene as a prime candidate for
the patient’s condition. This mutation is confirmed by Sanger DNA
sequencing and is found on the plus strand of hg38
chrX:153723153C>T that predicts to cause
NM_001256447.2:c.92G>A, p.Arg31Lys change (Fig. 2). This
novel variant has not been reported in Taiwan BioBank or any other
database. Even with careful analysis of the sequencing and optical
mapping data, no other disease-causing variant (including SNVs, small
indels, and structural variation) could be identified in the patient’sBCAP31 gene.