Methods and processes for non-invasive assessment of genetic variations

A system comprising:

• I. a sequencing module that performs a non-targeted massively parallel sequencing process to generate nucleic acid sequence reads from a test sample from a pregnant subject, wherein the sequence reads are reads of circulating cell-free nucleic acid from (i) a maternal genome and (ii) a fetal genome;
• and
• II. one or more microprocessors and memory, which memory comprises instructions executable by the one or more microprocessors, and which instructions executable by the one or more microprocessors are configured to:
• (a) map the nucleic acid sequence reads to genomic sections of a reference genome, count the nucleic acid sequence reads mapped to the genomic sections of the reference genome, and normalize the counts of the nucleic acid sequence reads mapped to the genomic sections of a reference genome, thereby providing normalized counts for the genomic sections, wherein the sequence reads that are mapped, counted, and normalized comprise reads of the maternal genome and the fetal genome;
• (b) identify a first elevation of the normalized counts for a first set of genomic sections significantly different than a second elevation of the normalized counts for a second set of genomic sections;
• (c) determine a copy number variation in the maternal genome for the first set of genomic sections based on the identified first and second elevations;
• (d) determine a categorization for the copy number variation in the maternal genome by comparing the first elevation to expected elevations for predetermined copy number variation categorizations;
• and
• (e) determine a fetal fraction of the circulating cell-free nucleic acid according to the first elevation and a deviation from an expected elevation of normalized counts for the categorization.