Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000328406 | SCV000334967 | uncertain significance | not provided | 2015-09-21 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV001166431 | SCV001328808 | uncertain significance | Acromesomelic dysplasia 1, Maroteaux type | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV001300728 | SCV001489877 | pathogenic | Acromesomelic dysplasia 1, Maroteaux type; Tall stature-scoliosis-macrodactyly of the great toes syndrome | 2022-10-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg776 amino acid residue in NPR2. Other variant(s) that disrupt this residue have been observed in individuals with NPR2-related conditions (PMID: 15146390), which suggests that this may be a clinically significant amino acid residue. 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 expected to disrupt NPR2 protein function. ClinVar contains an entry for this variant (Variation ID: 283086). This missense change has been observed in individuals with clinical features of autosomal recessive acromesomelic dysplasia (Invitae). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs780293535, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 776 of the NPR2 protein (p.Arg776Gln). |
| Blueprint Genetics | RCV000328406 | SCV001832300 | likely pathogenic | not provided | 2019-11-30 | criteria provided, single submitter | clinical testing |