Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV002472220 | SCV002769315 | uncertain significance | Hyperphosphatasia with intellectual disability syndrome 3 | 2020-05-21 | criteria provided, single submitter | clinical testing | A heterozygous missense variant was identified, NM_001346401.1(PGAP2):c.484C>T in exon 7 of 9 of the PGAP2 gene (NB: This variant is synonymous in alternative transcripts, including the predominant transcript, NM_001256240). This substitution is predicted to create a moderate amino acid change from proline to serine at position 162 of the protein, NP_001333330.1(PGAP2):p.(Pro162Ser). The proline at this position has low conservation (100 vertebrates, UCSC), and is not located within a known functional domain. In silico software predicts this variant to be benign (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD population database at a frequency of 0.0012% (3 heterozygotes, 0 homozygotes). The variant has not been previously reported in clinical cases. Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS) with LOW CLINICAL RELEVANCE. |