Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003006832 | SCV003721169 | uncertain significance | Inborn genetic diseases | 2021-12-13 | criteria provided, single submitter | clinical testing | The c.1655A>G (p.H552R) alteration is located in exon 10 (coding exon 10) of the NPR2 gene. This alteration results from a A to G substitution at nucleotide position 1655, causing the histidine (H) at amino acid position 552 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV005215963 | SCV005854597 | uncertain significance | Acromesomelic dysplasia 1, Maroteaux type; Tall stature-scoliosis-macrodactyly of the great toes syndrome | 2024-03-28 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 552 of the NPR2 protein (p.His552Arg). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with NPR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2376066). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NPR2 protein function with a negative predictive value of 80%. 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. |