ClinVar Miner

Submissions for variant NM_003995.4(NPR2):c.2321C>T (p.Ala774Val)

gnomAD frequency: 0.00004  dbSNP: rs369154896
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000513739 SCV000610029 uncertain significance not provided 2017-06-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001050909 SCV001215038 uncertain significance Acromesomelic dysplasia 1, Maroteaux type; Tall stature-scoliosis-macrodactyly of the great toes syndrome 2019-02-27 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 774 of the NPR2 protein (p.Ala774Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs369154896, ExAC 0.02%). This variant has not been reported in the literature in individuals with NPR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 445544). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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