Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics, |
RCV003994649 | SCV004812412 | uncertain significance | Autosomal recessive cerebellar ataxia-saccadic intrusion syndrome | 2022-04-01 | criteria provided, single submitter | clinical testing | This sequence change in VPS13D is predicted to replace methionine with arginine at codon 3252, p.(Met3252Arg). The methionine residue is highly conserved (100 vertebrates, UCSC), and is not in an annotated functional domain. There is a moderate physicochemical difference between methionine and arginine. This variant is absent from gnomAD v2,1 and v3.1. To our knowledge, this variant has not been reported in the literature in any individuals with VPS13D-releated disease. Multiple lines of computational evidence predict a deleterious effect for the missense substitution (3/4 algorithms). Based on the classification scheme RMH Modified ACMG Guidelines v1.5.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2_Supporting, PP3. |