Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000409359 | SCV000487297 | likely pathogenic | Metachromatic leukodystrophy | 2016-11-09 | criteria provided, single submitter | clinical testing | |
Molecular Genetics Laboratory, |
RCV000409359 | SCV000930529 | pathogenic | Metachromatic leukodystrophy | 2019-08-02 | criteria provided, single submitter | clinical testing | The Gln176Ter, a null variant (nonsense) affecting ARSA gene has been reported together with Arg293Ter in one Taiwanese patient with late infantile metachromatic leukodystrophy (Liaw et al., 2015), and was at extremely low frequency in ExAC (0.000009, 1/115950) and GnomAD_exome (0.000008, 2/246212). In our tested patient, Gln176Ter was found in the heterozygous state in unknown phase with a variant of uncertain significance, Arg313Gln. In summary, the Gln176Ter variant meets our criteria to be classified as pathogenic (Richards et al., 2015) based upon a known mechanism of disease, extremely low frequency and the previous reported evidence. |
Invitae | RCV000409359 | SCV002141338 | pathogenic | Metachromatic leukodystrophy | 2023-06-18 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 371662). This premature translational stop signal has been observed in individual(s) with late infantile metachromatic leukodystrophy (PMID: 26553228). This variant is present in population databases (rs762284875, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Gln176*) in the ARSA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARSA are known to be pathogenic (PMID: 8962139, 10477432). |