Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Hacettepe Genetic Diseases Diagnosis Center, |
RCV001262118 | SCV001245064 | likely pathogenic | Acromesomelic dysplasia 1, Maroteaux type | 2020-04-28 | criteria provided, single submitter | clinical testing | Molecular genetic analysis of the NPR2 gene identified a homozygous variant NM_003995.4:c.2720C>T (p.Thr907Met) in a patient with disproportionate short stature. This variant has previously been reported in sixteen patients of the five families diagnosed with Acromesomelic dysplasia, Maroteaux type (Khan et al., 2012). This variant is classified as likely pathogenic according to the ACMG guidelines and considered as disease causing by in silico analysis such as MutationTaster. |
Invitae | RCV001385134 | SCV001584890 | pathogenic | Acromesomelic dysplasia 1, Maroteaux type; Tall stature-scoliosis-macrodactyly of the great toes syndrome | 2022-08-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 873127). This missense change has been observed in individuals with autosomal recessive acromesomelic dysplasia, type Maroteaux (PMID: 22691581). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 907 of the NPR2 protein (p.Thr907Met). |
Blueprint Genetics | RCV001597245 | SCV001832276 | pathogenic | not provided | 2019-11-19 | criteria provided, single submitter | clinical testing | |
Lupski Lab, |
RCV001262118 | SCV002546521 | likely pathogenic | Acromesomelic dysplasia 1, Maroteaux type | 2022-06-07 | criteria provided, single submitter | research | |
3billion | RCV002283524 | SCV002572565 | likely pathogenic | Short stature with nonspecific skeletal abnormalities | 2022-09-01 | criteria provided, single submitter | clinical testing | This missense variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.94; 3Cnet: 0.21). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence for autosomal recessive NPR2-related disorder (ClinVar ID: VCV000873127). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |