Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Medical Genetics and Applied Genomics, |
RCV001268187 | SCV001446916 | likely pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001268187 | SCV002001628 | pathogenic | not provided | 2022-04-26 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge |
Victorian Clinical Genetics Services, |
RCV002471074 | SCV002769122 | pathogenic | Hypotonia, infantile, with psychomotor retardation and characteristic facies 3 | 2022-02-02 | 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 hypotonia, infantile, with psychomotor delay and characteristic facies 3 (MIM#616900). (I) 0106 - This gene is associated with autosomal recessive disease. (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) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (17 heterozygotes, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. These variants have been reported many times as pathogenic, and observed in individuals with intellectual disability and hypotonia syndrome (DECIPHER, PMID: 27040691). (SP) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. This variant has been reported as likely pathogenic, and observed in a single individual with global developmental delay (ClinVar, LOVD). (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) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |