Variant Synonymizer: Platform to identify mutations defined in different ways is available now!
Over 2,000 gene–disease validation summaries are now available—no login required!
A homozygous missense variant in VWA2, c.1336C>T (p.Arg446Cys) (PMID:29351342), was identified in a patient with congenital anomalies of the kidney and urinary tract (CAKUT). The affected individual, originating from a consanguineous descent, presents an autosomal recessive inheritance pattern. Although only one proband has been reported, the variant’s occurrence in the context of CAKUT provides an initial genetic link between VWA2 and the disease, warranting cautious consideration in diagnostic decision‑making.
Functional studies utilizing immunohistochemistry in neonatal mouse kidneys and in vitro assays demonstrated that the p.Arg446Cys variant alters VWA2 protein translocation and its interaction with FRAS1, suggesting a dose‑dependent neomorphic effect. These experimental findings, although stemming from a single patient report, enhance the overall evidence supporting the gene‑disease association. Key take‑home: despite limited genetic evidence, the robust functional data provided by the study supports the inclusion of VWA2 in diagnostic gene panels for CAKUT.
Gene–Disease AssociationLimitedA single proband with a homozygous missense variant in VWA2 associated with CAKUT provides preliminary evidence (PMID:29351342). Genetic EvidenceLimitedThe identification of the c.1336C>T (p.Arg446Cys) variant in one affected individual from a consanguineous family supports a genetic link, though the data is limited to a single case (PMID:29351342). Functional EvidenceModerateIn vitro and immunohistochemical studies demonstrate that the p.Arg446Cys alteration affects VWA2 protein translocation and its interaction with FRAS1, supporting a functional role in disease pathogenesis (PMID:29351342). |