Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Pathology and Laboratory Medicine, |
RCV001354523 | SCV001549164 | likely pathogenic | not provided | no assertion criteria provided | clinical testing | The PCNT p.E950* variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs1215854055) and in control databases in 1 of 251490 chromosomes at a frequency of 0.000003976 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the European (non-Finnish) population in 1 of 113764 chromosomes (freq: 0.000009), but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other, or South Asian populations. The c.2848G>T variant leads to a premature stop codon at position 950 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the PCNT gene are an established mechanism of disease in microcephalic osteodysplastic primordial dwarfism and are the type of variant expected to cause the disorder when found in the homozygous or compound heterozygous state. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic. |