Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001797037 | SCV002038566 | likely pathogenic | Shwachman-Diamond syndrome 1 | 2021-05-13 | criteria provided, single submitter | clinical testing | The SBDS c.653G>A (p.Arg218Gln) variant is a missense variant that is reported in three unrelated individuals with Shwachman-Diamond syndrome. Donadieu et al. (2012) identified one patient who carried the p.Arg218Gln variant in a presumed compound heterozygous state with a p.Cys84fs variant, which was noted to result from either c.258+2T>C or c.258+1G>A, while Ipatova et al. (2019) found two unrelated patients who carried the p.Arg218Gln variant in a presumed compound heterozygous state with a c.258+2T>C variant. The p.Arg218Gln variant is reported at a frequency of 0.000009 in the European (non-Finnish) population of the Genome Aggregation Database (version 2.1.1), though this is based on only a single allele in a region of good sequencing coverage, suggesting that the variant is rare. Weis at el. (2015) suggest that the highly conserved Arg218 residue may make electrostatic interactions with the tip of a helix portion of the protein to help provide stability during binding to EFL1. Multiple computational analyses suggest that the p.Arg218Gln variant would negatively impact the protein, though these predictions have not been experimentally confirmed. Based on the available evidence, the p.Arg218Gln variant is classified as likely pathogenic for Shwachman-Diamond syndrome. |
| Baylor Genetics | RCV003475094 | SCV004202338 | likely pathogenic | Aplastic anemia | 2023-08-01 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004801050 | SCV005422085 | uncertain significance | not specified | 2024-10-25 | criteria provided, single submitter | clinical testing | Variant summary: SBDS c.653G>A (p.Arg218Gln) results in a conservative amino acid change located in the Ribosome maturation protein SDO1/SBDS, C-terminal domain (IPR046928) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251282 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.653G>A in individuals affected with Shwachman-Diamond Syndrome 1 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1328553). Based on the evidence outlined above, the variant was classified as uncertain significance. |