Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Centre for Mendelian Genomics, |
RCV001198632 | SCV001369626 | likely pathogenic | Severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome | 2019-01-03 | criteria provided, single submitter | clinical testing | This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2. |
| Victorian Clinical Genetics Services, |
RCV001198632 | SCV002766914 | pathogenic | Severe growth deficiency-strabismus-extensive dermal melanocytosis-intellectual disability syndrome | 2022-09-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with neurodevelopmental disorder with microcephaly and gray sclerae (MIM#617051). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 34415064). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0703 - Other NMD-predicted variants comparable to the one identified in this case have moderate previous evidence for pathogenicity (DECIPHER, PMIDs: 34415064, 31444731). (SP) 0803 - This variant has limited previous evidence of pathogenicity in one unrelated individual. This variant has been classified as likely pathogenic by a clinical laboratory in ClinVar. This same individual with a neurodevelopmental disorder was also reported in a doctoral dissertation thesis, where they were reported to be compound heterozgous for this variant and a missense variant (Stojanović, 2020). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1205 - This variant has been shown to be maternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |