Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV001267728 | SCV001445983 | uncertain significance | Mulibrey nanism syndrome | 2020-11-16 | no assertion criteria provided | curation | The heterozygous c.1889+1G>A variant in PNPLA7 was identified by our study in the compound heterozygous state, along with another variant of unknown significance, in 1 individual with neurodevelopmental disease. The variant has not been previously reported in individuals with neurodevelopmental disease but has been identified in 0.011% (14/127748) of European non-Finnish chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs767961762). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. This variant occurs in the invariant region (+/- 1/2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. It is of note that loss of function of PNPLA7 in an autosomal recessive disease has not yet been established based on the criteria laid out in Tayoun, 2018 (PMID: 30192042). Furthermore, although this gene has been reported in association with neurodevelopmental disease, it currently has limited evidence for these associations. In summary, the clinical significance of the c.1889+1G>A variant is uncertain. |