Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000015026 | SCV002258550 | uncertain significance | Purine-nucleoside phosphorylase deficiency | 2021-11-16 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 13989). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individuals with clinical features of purine nucleoside phosphorylase deficiency (PMID: 9067751; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 174 of the PNP protein (p.Ala174Pro). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004700237 | SCV005205376 | likely pathogenic | Severe combined immunodeficiency disease | 2024-06-03 | criteria provided, single submitter | clinical testing | Variant summary: PNP c.520G>C (p.Ala174Pro) results in a non-conservative amino acid change located in the Nucleoside phosphorylase domain (IPR000845) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251466 control chromosomes (gnomAD). c.520G>C has been reported in the literature in homozygous- and compound heterozygous individuals affected with Severe Combined Immunodeficiency (Markert_1997, Suratannon_2020, Torun_2022, Barreiros_2022). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 9067751, 32373116, 35063692, 5503492). ClinVar contains an entry for this variant (Variation ID: 13989). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| OMIM | RCV000015026 | SCV000035282 | pathogenic | Purine-nucleoside phosphorylase deficiency | 1997-01-01 | no assertion criteria provided | literature only |