Discovery of heterozygous digenic deleterious variants in human NTD cases with spina bifida (i.e. PTK7/ SCRIB) and anencephaly (i.e. CELSR1/SCRIB; CELSR1/DVL3) strongly support the strategy of screening PCP genes to discover risk alleles contributing to human NTDs3,12. The gene discussed is DVL3; the disease is anencephaly.