Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics, |
RCV003994708 | SCV004812703 | uncertain significance | Charlevoix-Saguenay spastic ataxia | 2022-08-04 | criteria provided, single submitter | clinical testing | This sequence change in SACS is predicted to replace aspartic acid with glycine at codon 1261, p.(Asp1261Gly). The aspartic acid residue is moderately conserved (100 vertebrates, UCSC), and is not located in an annotated domain. There is a moderate physicochemical difference between aspartic acid and glycine. The highest population minor allele frequency in gnomAD v2.1 is 0.0009% (1/113,450 alleles) in the European (non-Finnish) population, which is consistent with recessive disease. To our knowledge, this variant has not been reported in the literature in any individuals with SACS-related disease. Multiple lines of computational evidence have conflicting predictions for the missense substitution (4/6 algorithms predict benign). 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. |