Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001378048 | SCV001575531 | likely pathogenic | Acromesomelic dysplasia 1, Maroteaux type; Tall stature-scoliosis-macrodactyly of the great toes syndrome | 2021-10-29 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 8 of the NPR2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NPR2 are known to be pathogenic (PMID: 15146390, 15572448, 16384845). This variant has not been reported in the literature in individuals affected with NPR2-related conditions. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1066921). |
Genome |
RCV001535596 | SCV001749604 | not provided | Acromesomelic dysplasia 1, Maroteaux type; Tall stature-scoliosis-macrodactyly of the great toes syndrome; Short stature with nonspecific skeletal abnormalities | no assertion provided | phenotyping only | Variant interpreted as Likely pathogenic and reported on 09-23-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |