Prediction of the caracteristics of CNV (PCC)

This tool was created to help clinicians estimate the potential impact of deletions in the genome (hg19 genomic map) on cognition based on the results of Huguet et al. (JAMA psychiatry 2018).

The tool estimates the loss of intellectual quotient (IQ) points related to a deletion as well as the estimated probability for that deletion to be de novo. The estimate is obtained from observations in two cohorts of the general population (N = 2,711) and two cohorts of neurodevelopmental disorder (N = 19,177). It is based on score of "probability that a gene is intolerant to a Loss of Function" (pLI)(Lek et al 2016).

This tool is not designed to predict the IQ of an individual. Instead it predicts the loss of IQ related to a genetic variant. This measure can be compared to the IQ of the patient who carries the deletion for consistency. For example, if a patient with an IQ of 55 carries a deletion associated with a loss of 40 points of IQ and this estimate is consistent with the cognitive impairment of the patient, the clinician could consider that this deletion represents a major diagnostic factor for this patient. If the deletion is associated with a 5 point decrease in IQ, it is reasonable to conclude that the variant is a minor factor in the patient’s cognitive deficit.

We will be updating this tool soon using a much larger dataset to reduce the confidence intervals of the predictions. We are extending these estimates to duplications and we are also investigating behavioural phenotypes independently of IQ.