Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV003472594 | SCV004202342 | pathogenic | Aplastic anemia | 2024-02-15 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV005036818 | SCV005667442 | pathogenic | Shwachman-Diamond syndrome 1; Aplastic anemia | 2024-03-27 | criteria provided, single submitter | clinical testing | |
Broad Center for Mendelian Genomics, |
RCV005254799 | SCV005907613 | pathogenic | Shwachman-Diamond syndrome 1 | 2025-02-07 | criteria provided, single submitter | curation | The p.Gln103ThrfsTer6 variant in SBDS has been reported, in the compound heterozygous state, in 1 individual with Shwachman-Diamond syndrome (PMID: 15776428) and has been identified in 0.003% (1/30612) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs749048311). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. The presence of a known pseudogene, SBDSP1, can impact the reliability of allele frequencies. This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 103 and leads to a premature termination codon 6 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the SBDS gene is an established disease mechanism in autosomal recessive Shwachman-Diamond syndrome. In summary, this variant meets criteria to be classified as Pathogenic for autosomal recessive Shwachman-Diamond syndrome. ACMG/AMP Criteria applied: PVS1, PM3, PM2_supporting (Richards 2015). |