Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000611427 | SCV000712872 | likely pathogenic | Brachyolmia | 2017-04-28 | criteria provided, single submitter | clinical testing | The p.Tyr74X (NM_001015880.1 c.222C>G) variant in PAPSS2 has not been reported i n individuals with brachyolmia. This variant has been identified in 0.029% (3/10 406) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://ex ac.broadinstitute.org; dbSNP rs374379931). This nonsense variant leads to a prem ature termination codon at position 74, which is predicted to lead to a truncate d or absent protein. Biallelic loss of function of the PAPSS2 gene has been asso ciated with brachyolmia. In summary, this variant meets criteria to be classifi ed as likely pathogenic for brachyolmia in an autosomal recessive manner based u pon its predicted null effect. |
Invitae | RCV001854143 | SCV002151812 | pathogenic | Spondyloepimetaphyseal dysplasia, PAPSS2 type | 2022-08-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 505568). This variant has not been reported in the literature in individuals affected with PAPSS2-related conditions. This variant is present in population databases (rs374379931, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Tyr74*) in the PAPSS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAPSS2 are known to be pathogenic (PMID: 22791835, 23633440). |
Prevention |
RCV003420054 | SCV004113728 | likely pathogenic | PAPSS2-related condition | 2022-10-24 | criteria provided, single submitter | clinical testing | The PAPSS2 c.222C>G variant is predicted to result in premature protein termination (p.Tyr74*). To our knowledge this variant has not been reported the literature in affected individuals. This variant is reported in 0.018% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-89472908-C-G). Nonsense variants in PAPSS2 are expected to be pathogenic, and premature termination variants have been reported in association with disease both up and downstream of amino acid 74. This variant is interpreted as likely pathogenic. |