Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Victorian Clinical Genetics Services, |
RCV004595036 | SCV005087065 | likely pathogenic | Shwachman-Diamond syndrome 1 | 2023-12-20 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Shwachman-Diamond syndrome (MIM#260400). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0205 - Variant is predicted to result in a truncated protein (premature termination codon is NOT located at least 54 nucleotides upstream of the final exon-exon junction) with less than 1/3 of the protein sequence affected. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0704 - Another variant comparable to the one identified in this case has limited previous evidence for pathogenicity. p.(Glu244_Gly245del) has been reported in a compound heterozygous individual with developmental delay, epilepsy and hypocellular marrow with mild dysplasia. She was initially diagnosed with dyskeratosis congenita due to short telemores (PMID: 28102861). In addition, p.(Glu244del) was identified in a compound heterozygous individual in whom SBDS gene sequencing was requested for, with no clinical information provided (GeneDx, personal communication). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1102 - Strong phenotype match for this individual. (SP) 1201 - Heterozygous variant detected in trans with a pathogenic heterozygous variant (NM_016038.2(SBDS):c.258+2T>C; p.(Cys84Tyrfs*4)) in a recessive disease. (SP) 1205 - This variant has been shown to be maternally inherited (by segregation analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |